186-587: A bacteriophage ( / b æ k ˈ t ɪər i oʊ f eɪ dʒ / ), also known informally as a phage ( / ˈ f eɪ dʒ / ), is a virus that infects and replicates within bacteria and archaea . The term is derived from Ancient Greek φαγεῖν (phagein) 'to devour' and bacteria . Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome , and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes (e.g. MS2 ) and as many as hundreds of genes . Phages replicate within
372-511: A Bosnian Serb named Gavrilo Princip assassinated Archduke Franz Ferdinand , heir to the Austro-Hungarian throne. Austria-Hungary held Serbia responsible, and declared war on 28 July. After Russia mobilised in Serbia's defence, Germany declared war on Russia and France , who had an alliance . The United Kingdom entered after Germany invaded Belgium , whose neutrality it guaranteed, and
558-630: A blue-water navy was vital for global power projection; Tirpitz had his books translated into German, while Wilhelm made them required reading for his advisors and senior military personnel. However, it was also an emotional decision, driven by Wilhelm's simultaneous admiration for the Royal Navy and desire to surpass it. Bismarck thought that the British would not interfere in Europe, as long as its maritime supremacy remained secure, but his dismissal in 1890 led to
744-555: A cyanophage containing 2-aminoadenine (Z) instead of adenine (A). The field of systems biology investigates the complex networks of interactions within an organism, usually using computational tools and modeling. For example, a phage genome that enters into a bacterial host cell may express hundreds of phage proteins which will affect the expression of numerous host genes or the host's metabolism . All of these complex interactions can be described and simulated in computer models. For instance, infection of Pseudomonas aeruginosa by
930-583: A grenade at the Archduke's car and injured two of his aides. The other assassins were also unsuccessful. An hour later, as Ferdinand was returning from visiting the injured officers in hospital, his car took a wrong turn into a street where Gavrilo Princip was standing. He fired two pistol shots, fatally wounding Ferdinand and his wife Sophie . According to historian Zbyněk Zeman , in Vienna "the event almost failed to make any impression whatsoever. On 28 and 29 June,
1116-536: A guerrilla warfare campaign and only surrendered two weeks after the armistice took effect in Europe. Before the war, Germany had attempted to use Indian nationalism and pan-Islamism to its advantage, a policy continued post-1914 by instigating uprisings in India , while the Niedermayer–Hentig Expedition urged Afghanistan to join the war on the side of Central Powers. However, contrary to British fears of
1302-406: A host cell is often forced to rapidly produce thousands of copies of the original virus. When not inside an infected cell or in the process of infecting a cell, viruses exist in the form of independent viral particles, or virions , consisting of (i) genetic material , i.e., long molecules of DNA or RNA that encode the structure of the proteins by which the virus acts; (ii) a protein coat,
1488-425: A virion , consists of nucleic acid surrounded by a protective coat of protein called a capsid . These are formed from protein subunits called capsomeres . Viruses can have a lipid "envelope" derived from the host cell membrane . The capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological distinction. Virally-coded protein subunits will self-assemble to form
1674-606: A basic optical microscope. In 2013, the Pandoravirus genus was discovered in Chile and Australia, and has genomes about twice as large as Megavirus and Mimivirus. All giant viruses have dsDNA genomes and they are classified into several families: Mimiviridae , Pithoviridae, Pandoraviridae , Phycodnaviridae , and the Mollivirus genus. Some viruses that infect Archaea have complex structures unrelated to any other form of virus, with
1860-418: A capsid diameter of 400 nm. Protein filaments measuring 100 nm project from the surface. The capsid appears hexagonal under an electron microscope, therefore the capsid is probably icosahedral. In 2011, researchers discovered the largest then known virus in samples of water collected from the ocean floor off the coast of Las Cruces, Chile. Provisionally named Megavirus chilensis , it can be seen with
2046-581: A capsid, in general requiring the presence of the virus genome. Complex viruses code for proteins that assist in the construction of their capsid. Proteins associated with nucleic acid are known as nucleoproteins , and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. The capsid and entire virus structure can be mechanically (physically) probed through atomic force microscopy . In general, there are five main morphological virus types: The poxviruses are large, complex viruses that have an unusual morphology. The viral genome
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#17328520219562232-467: A cell wall of polysaccharides , which are important virulence factors protecting bacterial cells against both immune host defenses and antibiotics . To enter a host cell, bacteriophages bind to specific receptors on the surface of bacteria, including lipopolysaccharides , teichoic acids , proteins , or even flagella . This specificity means a bacteriophage can infect only certain bacteria bearing receptors to which they can bind, which in turn, determines
2418-639: A cellular structure, which is often seen as the basic unit of life. Viruses do not have their own metabolism and require a host cell to make new products. They therefore cannot naturally reproduce outside a host cell —although some bacteria such as rickettsia and chlamydia are considered living organisms despite the same limitation. Accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells. They differ from autonomous growth of crystals as they inherit genetic mutations while being subject to natural selection. Virus self-assembly within host cells has implications for
2604-408: A change in policy and an Anglo-German naval arms race began. Despite the vast sums spent by Tirpitz, the launch of HMS Dreadnought in 1906 gave the British a technological advantage. Ultimately, the race diverted huge resources into creating a German navy large enough to antagonise Britain, but not defeat it; in 1911, Chancellor Theobald von Bethmann Hollweg acknowledged defeat, leading to
2790-423: A day). This proved effective for a very brief period, although the patient remained unresponsive and his health continued to worsen; soon isolates of a strain of A. baumannii were being collected from drainage of the cyst that showed resistance to this cocktail, and a second cocktail which was tested to be effective against this new strain was added, this time by intravenous (IV) injection as it had become clear that
2976-493: A different DNA (or RNA) molecule. This can occur when viruses infect cells simultaneously and studies of viral evolution have shown that recombination has been rampant in the species studied. Recombination is common to both RNA and DNA viruses. Coronaviruses have a single-strand positive-sense RNA genome. Replication of the genome is catalyzed by an RNA-dependent RNA polymerase . The mechanism of recombination used by coronaviruses likely involves template switching by
3162-592: A direct threat. The 1908–1909 Bosnian Crisis began when Austria annexed the former Ottoman territory of Bosnia and Herzegovina , which it had occupied since 1878. Timed to coincide with the Bulgarian Declaration of Independence from the Ottoman Empire, this unilateral action was denounced by the European powers, but accepted as there was no consensus on how to resolve the situation. Some historians see this as
3348-559: A few species, or broad for viruses capable of infecting many. Viral infections in animals provoke an immune response that usually eliminates the infecting virus. Immune responses can also be produced by vaccines , which confer an artificially acquired immunity to the specific viral infection. Some viruses, including those that cause HIV/AIDS , HPV infection , and viral hepatitis , evade these immune responses and result in chronic infections. Several classes of antiviral drugs have been developed. The English word "virus" comes from
3534-549: A fluid, by Wendell Meredith Stanley , and the invention of the electron microscope in 1931 allowed their complex structures to be visualised. Scientific opinions differ on whether viruses are a form of life or organic structures that interact with living organisms. They have been described as "organisms at the edge of life", since they resemble organisms in that they possess genes , evolve by natural selection , and reproduce by creating multiple copies of themselves through self-assembly. Although they have genes, they do not have
3720-467: A gap between the German armies as they closed on Paris. The French army, reinforced by the British expeditionary corps, seized this opportunity to counter-attack and pushed the German army 40 to 80 km back. Both armies were then so exhausted that no decisive move could be implemented, so they settled in trenches, with the vain hope of breaking through as soon as they could build local superiority. In 1911,
3906-445: A genome size of only two kilobases; the largest—the pandoraviruses —have genome sizes of around two megabases which code for about 2500 proteins. Virus genes rarely have introns and often are arranged in the genome so that they overlap . In general, RNA viruses have smaller genome sizes than DNA viruses because of a higher error-rate when replicating, and have a maximum upper size limit. Beyond this, errors when replicating render
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#17328520219564092-506: A ladder. The virus particles of some virus families, such as those belonging to the Hepadnaviridae , contain a genome that is partially double-stranded and partially single-stranded. For most viruses with RNA genomes and some with single-stranded DNA (ssDNA) genomes, the single strands are said to be either positive-sense (called the 'plus-strand') or negative-sense (called the 'minus-strand'), depending on if they are complementary to
4278-436: A life form, because they carry genetic material, reproduce, and evolve through natural selection , although they lack some key characteristics, such as cell structure, that are generally considered necessary criteria for defining life. Because they possess some but not all such qualities, viruses have been described as "organisms at the edge of life" and as replicators . Viruses spread in many ways. One transmission pathway
4464-472: A limited range of hosts and many are species-specific. Some, such as smallpox virus for example, can infect only one species—in this case humans, and are said to have a narrow host range . Other viruses, such as rabies virus, can infect different species of mammals and are said to have a broad range. The viruses that infect plants are harmless to animals, and most viruses that infect other animals are harmless to humans. The host range of some bacteriophages
4650-400: A portion of the cell membrane before inserting their genetic material. Within minutes, bacterial ribosomes start translating viral mRNA into protein. For RNA-based phages, RNA replicase is synthesized early in the process. Proteins modify the bacterial RNA polymerase so it preferentially transcribes viral mRNA. The host's normal synthesis of proteins and nucleic acids is disrupted, and it
4836-540: A possibility. This was accentuated by British and Russian support for France against Germany during the 1911 Agadir Crisis . German economic and industrial strength continued to expand rapidly post-1871. Backed by Wilhelm II, Admiral Alfred von Tirpitz sought to use this growth to build an Imperial German Navy , that could compete with the British Royal Navy . This policy was based on the work of US naval author Alfred Thayer Mahan , who argued that possession of
5022-411: A possible therapy against multi-drug-resistant strains of many bacteria (see phage therapy ). Bacteriophages are known to interact with the immune system both indirectly via bacterial expression of phage-encoded proteins and directly by influencing innate immunity and bacterial clearance. Phage–host interactions are becoming increasingly important areas of research. Bacteriophages occur abundantly in
5208-408: A prime target for natural selection. Segmented genomes confer evolutionary advantages; different strains of a virus with a segmented genome can shuffle and combine genes and produce progeny viruses (or offspring) that have unique characteristics. This is called reassortment or 'viral sex'. Genetic recombination is a process by which a strand of DNA (or RNA) is broken and then joined to the end of
5394-799: A revolt in India, the outbreak of the war saw a reduction in nationalist activity. Leaders from the Indian National Congress and other groups believed support for the British war effort would hasten Indian Home Rule , a promise allegedly made explicit in 1917 by Edwin Montagu , the Secretary of State for India . In 1914, the British Indian Army was larger than the British Army itself, and between 1914 and 1918 an estimated 1.3 million Indian soldiers and labourers served in Europe, Africa, and
5580-504: A significant escalation, ending any chance of Austria cooperating with Russia in the Balkans, while also damaging diplomatic relations between Serbia and Italy. Tensions increased after the 1911–1912 Italo-Turkish War demonstrated Ottoman weakness and led to the formation of the Balkan League , an alliance of Serbia, Bulgaria, Montenegro , and Greece . The League quickly overran most of
5766-412: A single viral particle that is released from the cell and is capable of infecting other cells of the same type. Viruses are found wherever there is life and have probably existed since living cells first evolved . The origin of viruses is unclear because they do not form fossils, so molecular techniques are used to infer how they arose. In addition, viral genetic material occasionally integrates into
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5952-456: A small part of the total diversity of viruses has been studied. As of 2022, 6 realms, 10 kingdoms, 17 phyla, 2 subphyla, 40 classes, 72 orders, 8 suborders, 264 families, 182 subfamilies , 2,818 genera, 84 subgenera , and 11,273 species of viruses have been defined by the ICTV. The general taxonomic structure of taxon ranges and the suffixes used in taxonomic names are shown hereafter. As of 2022,
6138-471: A war on two fronts; the Schlieffen Plan envisaged using 80% of the army to defeat France, then switching to Russia. Since this required them to move quickly, mobilization orders were issued that afternoon. Once the German ultimatum to Russia expired on the morning of 1 August, the two countries were at war. At a meeting on 29 July, the British cabinet had narrowly decided its obligations to Belgium under
6324-402: A weak Ottoman government, rather than an ambitious Slav power like Bulgaria . Russia had ambitions in northeastern Anatolia while its clients had overlapping claims in the Balkans. These competing interests divided Russian policy-makers and added to regional instability. Austrian statesmen viewed the Balkans as essential for the continued existence of their Empire and saw Serbian expansion as
6510-451: A whole, the Somme offensive led to an estimated 420,000 British casualties, along with 200,000 French and 500,000 Germans. The diseases that emerged in the trenches were a major killer on both sides. The living conditions led to disease and infection, such as trench foot , lice , typhus , trench fever , and the ' Spanish flu '. At the start of the war, German cruisers were scattered across
6696-605: A wide diversity of sizes and shapes, called ' morphologies '. In general, viruses are much smaller than bacteria and more than a thousand bacteriophage viruses would fit inside an Escherichia coli bacterium's cell. Many viruses that have been studied are spherical and have a diameter between 20 and 300 nanometres . Some filoviruses , which are filaments, have a total length of up to 1400 nm; their diameters are only about 80 nm. Most viruses cannot be seen with an optical microscope , so scanning and transmission electron microscopes are used to visualise them. To increase
6882-553: A wide variety of unusual shapes, ranging from spindle-shaped structures to viruses that resemble hooked rods, teardrops or even bottles. Other archaeal viruses resemble the tailed bacteriophages, and can have multiple tail structures. An enormous variety of genomic structures can be seen among viral species ; as a group, they contain more structural genomic diversity than plants, animals, archaea, or bacteria. There are millions of different types of viruses, although fewer than 7,000 types have been described in detail. As of January 2021,
7068-530: Is a clean label processing aid and is included in USDA. Research in the field of food safety is continuing to see if lytic phages are a viable option to control other food-borne pathogens in various food products. Bacteriophages, including those specific to Escherichia coli , have been employed as indicators of fecal contamination in water sources. Due to their shared structural and biological characteristics, coliphages can serve as proxies for viral fecal contamination and
7254-416: Is a feature of many bacterial and some animal viruses. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host's chromosome. The viral genome is then known as a " provirus " or, in the case of bacteriophages a " prophage ". Whenever the host divides, the viral genome is also replicated. The viral genome is mostly silent within
7440-405: Is a major change in the genome of the virus. This can be a result of recombination or reassortment . The Influenza A virus is highly prone to reassortment; occasionally this has resulted in novel strains which have caused pandemics . RNA viruses often exist as quasispecies or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are
7626-400: Is associated with proteins within a central disc structure known as a nucleoid . The nucleoid is surrounded by a membrane and two lateral bodies of unknown function. The virus has an outer envelope with a thick layer of protein studded over its surface. The whole virion is slightly pleomorphic , ranging from ovoid to brick-shaped. Mimivirus is one of the largest characterised viruses, with
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7812-439: Is caused by cessation of its normal activities because of suppression by virus-specific proteins, not all of which are components of the virus particle. The distinction between cytopathic and harmless is gradual. Some viruses, such as Epstein–Barr virus , can cause cells to proliferate without causing malignancy, while others, such as papillomaviruses , are established causes of cancer. Some viruses cause no apparent changes to
7998-701: Is controversy over whether the bornavirus , previously thought to cause neurological diseases in horses, could be responsible for psychiatric illnesses in humans. World War I World War I or the First World War (28 July 1914 – 11 November 1918), also known as the Great War , was a global conflict between two coalitions: the Allies (or Entente) and the Central Powers . Fighting took place mainly in Europe and
8184-512: Is correct. It seems unlikely that all currently known viruses have a common ancestor, and viruses have probably arisen numerous times in the past by one or more mechanisms. The first evidence of the existence of viruses came from experiments with filters that had pores small enough to retain bacteria. In 1892, Dmitri Ivanovsky used one of these filters to show that sap from a diseased tobacco plant remained infectious to healthy tobacco plants despite having been filtered. Martinus Beijerinck called
8370-498: Is first recorded in 1728, long before the discovery of viruses by Dmitri Ivanovsky in 1892. The English plural is viruses (sometimes also vira ), whereas the Latin word is a mass noun , which has no classically attested plural ( vīra is used in Neo-Latin ). The adjective viral dates to 1948. The term virion (plural virions ), which dates from 1959, is also used to refer to
8556-540: Is forced to manufacture viral products instead. These products go on to become part of new virions within the cell, helper proteins that contribute to the assemblage of new virions, or proteins involved in cell lysis . In 1972, Walter Fiers ( University of Ghent , Belgium ) was the first to establish the complete nucleotide sequence of a gene and in 1976, of the viral genome of bacteriophage MS2 . Some dsDNA bacteriophages encode ribosomal proteins, which are thought to modulate protein translation during phage infection. In
8742-607: Is identical in sequence to the viral mRNA and is thus a coding strand, while negative-sense viral ssDNA is complementary to the viral mRNA and is thus a template strand. Several types of ssDNA and ssRNA viruses have genomes that are ambisense in that transcription can occur off both strands in a double-stranded replicative intermediate. Examples include geminiviruses , which are ssDNA plant viruses and arenaviruses , which are ssRNA viruses of animals. Genome size varies greatly between species. The smallest—the ssDNA circoviruses, family Circoviridae —code for only two proteins and have
8928-447: Is initiated and the tail contracts, possibly with the help of ATP present in the tail, injecting genetic material through the bacterial membrane. The injection is accomplished through a sort of bending motion in the shaft by going to the side, contracting closer to the cell and pushing back up. Podoviruses lack an elongated tail sheath like that of a myovirus, so instead, they use their small, tooth-like tail fibers enzymatically to degrade
9114-503: Is known, however, that from 1908 to 1913, military spending by the six major European powers increased by over 50% in real terms. The years before 1914 were marked by a series of crises in the Balkans, as other powers sought to benefit from the Ottoman decline. While Pan-Slavic and Orthodox Russia considered itself the protector of Serbia and other Slav states, they preferred the strategically vital Bosporus straits to be controlled by
9300-431: Is limited to a single strain of bacteria and they can be used to trace the source of outbreaks of infections by a method called phage typing . The complete set of viruses in an organism or habitat is called the virome ; for example, all human viruses constitute the human virome . A novel virus is one that has not previously been recorded. It can be a virus that is isolated from its natural reservoir or isolated as
9486-506: Is not identical to that of the temperate phage going dormant and usually is temporary. In contrast, the lysogenic cycle does not result in immediate lysing of the host cell. Those phages able to undergo lysogeny are known as temperate phages . Their viral genome will integrate with host DNA and replicate along with it, relatively harmlessly, or may even become established as a plasmid . The virus remains dormant until host conditions deteriorate, perhaps due to depletion of nutrients, then,
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#17328520219569672-519: Is one such mechanism as are retrons and the anti-toxin system encoded by them. The Thoeris defense system is known to deploy a unique strategy for bacterial antiphage resistance via NAD+ degradation. Virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism . Viruses infect all life forms , from animals and plants to microorganisms , including bacteria and archaea . Viruses are found in almost every ecosystem on Earth and are
9858-462: Is some evidence that this unusual component is a mechanism to evade bacterial defense mechanisms such as restriction endonucleases and CRISPR/Cas systems which evolved to recognize and cleave sequences within invading phages, thereby inactivating them. Other phages have long been known to use unusual nucleotides. In 1963, Takahashi and Marmur identified a Bacillus phage that has dU substituting dT in its genome, and in 1977, Kirnos et al. identified
10044-475: Is through disease-bearing organisms known as vectors : for example, viruses are often transmitted from plant to plant by insects that feed on plant sap , such as aphids ; and viruses in animals can be carried by blood-sucking insects. Many viruses spread in the air by coughing and sneezing, including influenza viruses , SARS-CoV-2 , chickenpox , smallpox , and measles . Norovirus and rotavirus , common causes of viral gastroenteritis , are transmitted by
10230-558: The Schutzkorps was established, and carried out the persecution of Serbs. The assassination initiated the July Crisis, a month of diplomatic manoeuvring between Austria-Hungary, Germany, Russia, France and Britain. Believing that Serbian intelligence helped organise Franz Ferdinand's murder, Austrian officials wanted to use the opportunity to end their interference in Bosnia and saw war as
10416-626: The World War . In August 1914, the magazine The Independent wrote "This is the Great War. It names itself". In October 1914, the Canadian magazine Maclean's similarly wrote, "Some wars name themselves. This is the Great War." Contemporary Europeans also referred to it as " the war to end war " and it was also described as "the war to end all wars" due to their perception of its unparalleled scale, devastation, and loss of life. The first recorded use of
10602-400: The capsid , which surrounds and protects the genetic material; and in some cases (iii) an outside envelope of lipids . The shapes of these virus particles range from simple helical and icosahedral forms to more complex structures. Most virus species have virions too small to be seen with an optical microscope and are one-hundredth the size of most bacteria. The origins of viruses in
10788-665: The Australian Naval and Military Expeditionary Force landed on the island of New Britain , then part of German New Guinea . On 28 October, the German cruiser SMS Emden sank the Russian cruiser Zhemchug in the Battle of Penang . Japan declared war on Germany before seizing territories in the Pacific, which later became the South Seas Mandate , as well as German Treaty ports on
10974-474: The CD4 molecule—a chemokine receptor —which is most commonly found on the surface of CD4+ T-Cells . This mechanism has evolved to favour those viruses that infect only cells in which they are capable of replication. Attachment to the receptor can induce the viral envelope protein to undergo changes that result in the fusion of viral and cellular membranes, or changes of non-enveloped virus surface proteins that allow
11160-540: The International Committee on Taxonomy of Viruses (ICTV) was formed. The system proposed by Lwoff, Horne and Tournier was initially not accepted by the ICTV because the small genome size of viruses and their high rate of mutation made it difficult to determine their ancestry beyond order. As such, the Baltimore classification system has come to be used to supplement the more traditional hierarchy. Starting in 2018,
11346-675: The Latin vīrus , which refers to poison and other noxious liquids. Vīrus comes from the same Indo-European root as Sanskrit viṣa , Avestan vīša , and Ancient Greek ἰός ( iós ), which all mean "poison". The first attested use of "virus" in English appeared in 1398 in John Trevisa 's translation of Bartholomeus Anglicus 's De Proprietatibus Rerum . Virulent , from Latin virulentus ('poisonous'), dates to c. 1400 . A meaning of 'agent that causes infectious disease'
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#173285202195611532-619: The Middle East , as well as in parts of Africa and the Asia-Pacific , and in Europe was characterised by trench warfare ; the widespread use of artillery , machine guns, and chemical weapons (gas); and the introductions of tanks and aircraft . World War I was one of the deadliest conflicts in history , resulting in an estimated 10 million military dead and more than 20 million wounded , plus some 10 million civilian dead from causes including genocide . The movement of large numbers of people
11718-484: The NCBI Virus genome database has more than 193,000 complete genome sequences, but there are doubtlessly many more to be discovered. A virus has either a DNA or an RNA genome and is called a DNA virus or an RNA virus , respectively. Most viruses have RNA genomes. Plant viruses tend to have single-stranded RNA genomes and bacteriophages tend to have double-stranded DNA genomes. Viral genomes are circular, as in
11904-791: The Nobel Prize in Physiology or Medicine for their discoveries of the replication of viruses and their genetic structure. Specifically the work of Hershey, as contributor to the Hershey–Chase experiment in 1952, provided convincing evidence that DNA, not protein, was the genetic material of life. Delbrück and Luria carried out the Luria–Delbrück experiment which demonstrated statistically that mutations in bacteria occur randomly and thus follow Darwinian rather than Lamarckian principles. Phages were discovered to be antibacterial agents and were used in
12090-790: The Red Army . However, they were abandoned for general use in the West for several reasons: The use of phages has continued since the end of the Cold War in Russia, Georgia, and elsewhere in Central and Eastern Europe. The first regulated, randomized, double-blind clinical trial was reported in the Journal of Wound Care in June 2009, which evaluated the safety and efficacy of a bacteriophage cocktail to treat infected venous ulcers of
12276-706: The Rüstungswende or 'armaments turning point', when he switched expenditure from the navy to the army. This decision was not driven by a reduction in political tensions but by German concern over Russia's quick recovery from its defeat in the Russo-Japanese War and subsequent 1905 Russian Revolution . Economic reforms led to a significant post-1908 expansion of railways and transportation infrastructure, particularly in its western border regions. Since Germany and Austria-Hungary relied on faster mobilisation to compensate for their numerical inferiority compared to Russia,
12462-491: The T4 phage , bacterial cells are broken open (lysed) and destroyed after immediate replication of the virion. As soon as the cell is destroyed, the phage progeny can find new hosts to infect. Lytic phages are more suitable for phage therapy . Some lytic phages undergo a phenomenon known as lysis inhibition, where completed phage progeny will not immediately lyse out of the cell if extracellular phage concentrations are high. This mechanism
12648-784: The United States entered the war on the Allied side following Germany's resumption of unrestricted submarine warfare against Atlantic shipping. Later that year, the Bolsheviks seized power in the Russian October Revolution , and Soviet Russia signed an armistice with the Central Powers in December, followed by a separate peace in March 1918. That month, Germany launched an offensive in
12834-539: The common cold , influenza , chickenpox , and cold sores . Many serious diseases such as rabies , Ebola virus disease , AIDS (HIV) , avian influenza , and SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of virulence . Other diseases are under investigation to discover if they have a virus as the causative agent, such as the possible connection between human herpesvirus 6 (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome . There
13020-461: The dysentery bacillus". For d'Hérelle, there was no question as to the nature of his discovery: "In a flash I had understood: what caused my clear spots was in fact an invisible microbe... a virus parasitic on bacteria." D'Hérelle called the virus a bacteriophage, a bacterium-eater (from the Greek phagein , meaning "to devour"). He also recorded a dramatic account of a man suffering from dysentery who
13206-454: The endogenous phages (known as prophages ) become active. At this point they initiate the reproductive cycle, resulting in lysis of the host cell. As the lysogenic cycle allows the host cell to continue to survive and reproduce, the virus is replicated in all offspring of the cell. An example of a bacteriophage known to follow the lysogenic cycle and the lytic cycle is the phage lambda of E. coli. Sometimes prophages may provide benefits to
13392-407: The evolutionary history of life are still unclear. Some viruses may have evolved from plasmids , which are pieces of DNA that can move between cells. Other viruses may have evolved from bacteria. In evolution, viruses are an important means of horizontal gene transfer , which increases genetic diversity in a way analogous to sexual reproduction . Viruses are considered by some biologists to be
13578-422: The faecal–oral route , passed by hand-to-mouth contact or in food or water. The infectious dose of norovirus required to produce infection in humans is fewer than 100 particles. HIV is one of several viruses transmitted through sexual contact and by exposure to infected blood. The variety of host cells that a virus can infect is called its host range : this is narrow for viruses specialized to infect only
13764-430: The germline of the host organisms, by which they can be passed on vertically to the offspring of the host for many generations. This provides an invaluable source of information for paleovirologists to trace back ancient viruses that existed as far back as millions of years ago. There are three main hypotheses that aim to explain the origins of viruses: In the past, there were problems with all of these hypotheses:
13950-480: The hydrophone and depth charges were introduced, destroyers could potentially successfully attack a submerged submarine. Convoys slowed the flow of supplies since ships had to wait as convoys were assembled; the solution was an extensive program of building new freighters. Troopships were too fast for the submarines and did not travel the North Atlantic in convoys. The U-boats sunk more than 5,000 Allied ships, at
14136-454: The polyomaviruses , or linear, as in the adenoviruses . The type of nucleic acid is irrelevant to the shape of the genome. Among RNA viruses and certain DNA viruses, the genome is often divided into separate parts, in which case it is called segmented. For RNA viruses, each segment often codes for only one protein and they are usually found together in one capsid. All segments are not required to be in
14322-789: The tank . After the First Battle of the Marne in September 1914, Allied and German forces unsuccessfully tried to outflank each other, a series of manoeuvres later known as the " Race to the Sea ". By the end of 1914, the opposing forces confronted each other along an uninterrupted line of entrenched positions from the Channel to the Swiss border. Since the Germans were normally able to choose where to stand, they generally held
14508-447: The three domains . This discovery has led modern virologists to reconsider and re-evaluate these three classical hypotheses. The evidence for an ancestral world of RNA cells and computer analysis of viral and host DNA sequences give a better understanding of the evolutionary relationships between different viruses and may help identify the ancestors of modern viruses. To date, such analyses have not proved which of these hypotheses
14694-588: The 1839 Treaty of London did not require it to oppose a German invasion with military force; however, Prime Minister Asquith and his senior Cabinet ministers were already committed to supporting France, the Royal Navy had been mobilised, and public opinion was strongly in favour of intervention. On 31 July, Britain sent notes to Germany and France, asking them to respect Belgian neutrality; France pledged to do so, but Germany did not reply. Aware of German plans to attack through Belgium, French Commander-in-Chief Joseph Joffre asked his government for permission to cross
14880-548: The 1879 Dual Alliance , which became the Triple Alliance when Italy joined in 1882. For Bismarck, the purpose of these agreements was to isolate France by ensuring the three Empires resolve any disputes between themselves. In 1887, Bismarck set up the Reinsurance Treaty , a secret agreement between Germany and Russia to remain neutral if either were attacked by France or Austria-Hungary. For Bismarck, peace with Russia
15066-441: The 1913 Treaty of London , which had created an independent Albania while enlarging the territories of Bulgaria, Serbia, Montenegro and Greece. However, disputes between the victors sparked the 33-day Second Balkan War , when Bulgaria attacked Serbia and Greece on 16 June 1913; it was defeated, losing most of Macedonia to Serbia and Greece, and Southern Dobruja to Romania. The result was that even countries which benefited from
15252-556: The Austrians and Serbs clashed at the battles of the Cer and Kolubara ; over the next two weeks, Austrian attacks were repulsed with heavy losses. As a result, Austria had to keep sizeable forces on the Serbian front, weakening their efforts against Russia. Serbia's victory against Austria-Hungary in the 1914 invasion has been called one of the major upset victories of the twentieth century. In 1915,
15438-642: The Austrians briefly occupied the Serbian capital, Belgrade . A Serbian counter-attack in the Battle of Kolubara succeeded in driving them from the country by the end of 1914. For the first 10 months of 1915, Austria-Hungary used most of its military reserves to fight Italy. German and Austro-Hungarian diplomats scored a coup by persuading Bulgaria to join the attack on Serbia. The Austro-Hungarian provinces of Slovenia , Croatia and Bosnia provided troops for Austria-Hungary. Montenegro allied itself with Serbia. Bulgaria declared war on Serbia on 14 October 1915 and joined in
15624-547: The Balkan Wars, such as Serbia and Greece, felt cheated of their "rightful gains", while for Austria it demonstrated the apparent indifference with which other powers viewed their concerns, including Germany. This complex mix of resentment, nationalism and insecurity helps explain why the pre-1914 Balkans became known as the " powder keg of Europe ". On 28 June 1914, Archduke Franz Ferdinand of Austria , heir presumptive to Emperor Franz Joseph I of Austria , visited Sarajevo ,
15810-655: The Brown Institution of London, discovered a small agent that infected and killed bacteria. He believed the agent must be one of the following: Twort's research was interrupted by the onset of World War I , as well as a shortage of funding and the discoveries of antibiotics. Independently, French-Canadian microbiologist Félix d'Hérelle , working at the Pasteur Institute in Paris , announced on 3 September 1917 that he had discovered "an invisible, antagonistic microbe of
15996-404: The Central Powers. However, the pro-German King Constantine I dismissed the pro-Allied government of Eleftherios Venizelos before the Allied expeditionary force arrived. The Macedonian front was at first mostly static. French and Serbian forces retook limited areas of Macedonia by recapturing Bitola on 19 November 1916 following the costly Monastir offensive , which brought stabilisation of
16182-625: The Chinese Shandong peninsula at Tsingtao . After Vienna refused to withdraw its cruiser SMS Kaiserin Elisabeth from Tsingtao, Japan declared war on Austria-Hungary, and the ship was sunk in November 1914. Within a few months, Allied forces had seized all German territories in the Pacific, leaving only isolated commerce raiders and a few holdouts in New Guinea. Some of the first clashes of
16368-613: The German High Seas Fleet was confined to port. German U-boats attempted to cut the supply lines between North America and Britain. The nature of submarine warfare meant that attacks often came without warning, giving the crews of the merchant ships little hope of survival. The United States launched a protest, and Germany changed its rules of engagement. After the sinking of the passenger ship RMS Lusitania in 1915, Germany promised not to target passenger liners, while Britain armed its merchant ships, placing them beyond
16554-623: The German Army increased in size from 1908 to 1914, he changed the allocation of forces between the two wings to 70:30. He also considered Dutch neutrality essential for German trade and cancelled the incursion into the Netherlands, which meant any delays in Belgium threatened the viability of the plan. Historian Richard Holmes argues that these changes meant the right wing was not strong enough to achieve decisive success. The initial German advance in
16740-724: The German right wing would sweep through the Netherlands and Belgium , then swing south, encircling Paris and trapping the French army against the Swiss border. The plan's creator, Alfred von Schlieffen , head of the German General Staff from 1891 to 1906, estimated that this would take six weeks, after which the German army would transfer to the East and defeat the Russians. The plan was substantially modified by his successor, Helmuth von Moltke
16926-480: The Germans bled heavily as well, with anywhere from 700,000 to 975,000 casualties between the two combatants. Verdun became a symbol of French determination and self-sacrifice. The Battle of the Somme was an Anglo-French offensive from July to November 1916. The opening day on 1 July 1916 was the bloodiest single day in the history of the British Army , which suffered 57,500 casualties, including 19,200 dead. As
17112-527: The ICTV began to acknowledge deeper evolutionary relationships between viruses that have been discovered over time and adopted a 15-rank classification system ranging from realm to species. Additionally, some species within the same genus are grouped into a genogroup . The ICTV developed the current classification system and wrote guidelines that put a greater weight on certain virus properties to maintain family uniformity. A unified taxonomy (a universal system for classifying viruses) has been established. Only
17298-675: The Middle East. In all, 140,000 soldiers served on the Western Front and nearly 700,000 in the Middle East, with 47,746 killed and 65,126 wounded. The suffering engendered by the war, as well as the failure of the British government to grant self-government to India afterward, bred disillusionment, resulting in the campaign for full independence led by Mahatma Gandhi . Pre-war military tactics that had emphasised open warfare and individual riflemen proved obsolete when confronted with conditions prevailing in 1914. Technological advances allowed
17484-709: The Ottomans joined the Central Powers in November. Germany's strategy in 1914 was to quickly defeat France, then to transfer its forces to the east, but its advance was halted in September , and by the end of the year the Western Front consisted of a continuous line of trenches stretching from the English Channel to Switzerland. The Eastern Front was more dynamic, but neither side gained a decisive advantage, despite costly offensives. Italy , Bulgaria , Romania , Greece and others joined in from 1915 onward. In April 1917,
17670-598: The Ottomans' territory in the Balkans during the 1912–1913 First Balkan War , much to the surprise of outside observers. The Serbian capture of ports on the Adriatic resulted in partial Austrian mobilisation, starting on 21 November 1912, including units along the Russian border in Galicia . The Russian government decided not to mobilise in response, unprepared to precipitate a war. The Great Powers sought to re-assert control through
17856-606: The Russian Stavka agreed with the French to attack Germany within fifteen days of mobilisation, ten days before the Germans had anticipated, although it meant the two Russian armies that entered East Prussia on 17 August did so without many of their support elements. By the end of 1914, German troops held strong defensive positions inside France, controlled the bulk of France's domestic coalfields, and inflicted 230,000 more casualties than it lost itself. However, communications problems and questionable command decisions cost Germany
18042-529: The Serbian retreat toward the Adriatic coast in the Battle of Mojkovac on 6–7 January 1916, but ultimately the Austrians also conquered Montenegro. The surviving Serbian soldiers were evacuated to Greece. After the conquest, Serbia was divided between Austro-Hungary and Bulgaria. In late 1915, a Franco-British force landed at Salonica in Greece to offer assistance and to pressure its government to declare war against
18228-582: The West was very successful. By the end of August, the Allied left, which included the British Expeditionary Force (BEF), was in full retreat , and the French offensive in Alsace-Lorraine was a disastrous failure, with casualties exceeding 260,000. German planning provided broad strategic instructions while allowing army commanders considerable freedom in carrying them out at the front, but von Kluck used this freedom to disobey orders, opening
18414-480: The Younger . Under Schlieffen, 85% of German forces in the west were assigned to the right wing, with the remainder holding along the frontier. By keeping his left-wing deliberately weak, he hoped to lure the French into an offensive into the "lost provinces" of Alsace-Lorraine , which was the strategy envisaged by their Plan XVII . However, Moltke grew concerned that the French might push too hard on his left flank and as
18600-446: The aggressor, German Chancellor Bethmann Hollweg delayed the commencement of war preparations until 31 July. That afternoon, the Russian government were handed a note requiring them to "cease all war measures against Germany and Austria-Hungary" within 12 hours. A further German demand for neutrality was refused by the French who ordered general mobilization but delayed declaring war. The German General Staff had long assumed they faced
18786-466: The attack by the Austro-Hungarian army under Mackensen's army of 250,000 that was already underway. Serbia was conquered in a little more than a month, as the Central Powers, now including Bulgaria, sent in 600,000 troops in total. The Serbian army, fighting on two fronts and facing certain defeat, retreated into northern Albania . The Serbs suffered defeat in the Battle of Kosovo . Montenegro covered
18972-499: The bacteriophage Φ3T makes a short viral protein that signals other bacteriophages to lie dormant instead of killing the host bacterium. Arbitrium is the name given to this protein by the researchers who discovered it. Given the millions of different phages in the environment, phage genomes come in a variety of forms and sizes. RNA phages such as MS2 have the smallest genomes, with only a few kilobases. However, some DNA phages such as T4 may have large genomes with hundreds of genes;
19158-420: The bacterium following the injection of their genome into its cytoplasm . Bacteriophages are among the most common and diverse entities in the biosphere . Bacteriophages are ubiquitous viruses, found wherever bacteria exist. It is estimated there are more than 10 bacteriophages on the planet, more than every other organism on Earth, including bacteria, combined. Viruses are the most abundant biological entity in
19344-484: The basis of similarities. In 1962, André Lwoff , Robert Horne , and Paul Tournier were the first to develop a means of virus classification, based on the Linnaean hierarchical system. This system based classification on phylum , class , order , family , genus , and species . Viruses were grouped according to their shared properties (not those of their hosts) and the type of nucleic acid forming their genomes. In 1966,
19530-535: The best way of achieving this. However, the Foreign Ministry had no solid proof of Serbian involvement. On 23 July, Austria delivered an ultimatum to Serbia, listing ten demands made intentionally unacceptable to provide an excuse for starting hostilities. Serbia ordered general mobilization on 25 July, but accepted all the terms, except for those empowering Austrian representatives to suppress "subversive elements" inside Serbia, and take part in
19716-419: The biofilm matrix, phage structural proteins, and the enzymes responsible for lysis of the bacterial cell wall. There have been results showing that T4 phages that are small in size and short-tailed can be helpful in detecting E. coli in the human body. Therapeutic efficacy of a phage cocktail was evaluated in a mouse model with nasal infection of multi-drug-resistant (MDR) A. baumannii . Mice treated with
19902-541: The biosphere, with different genomes and lifestyles. Phages are classified by the International Committee on Taxonomy of Viruses (ICTV) according to morphology and nucleic acid. It has been suggested that members of Picobirnaviridae infect bacteria, but not mammals. There are also many unassigned genera of the class Leviviricetes : Chimpavirus , Hohglivirus , Mahrahvirus , Meihzavirus , Nicedsevirus , Sculuvirus , Skrubnovirus , Tetipavirus and Winunavirus containing linear ssRNA genomes and
20088-483: The border and pre-empt such a move. To avoid violating Belgian neutrality, he was told any advance could come only after a German invasion. Instead, the French cabinet ordered its Army to withdraw 10 km behind the German frontier, to avoid provoking war. On 2 August, Germany occupied Luxembourg and exchanged fire with French units when German patrols entered French territory; on 3 August, they declared war on France and demanded free passage across Belgium, which
20274-480: The campaign saw the first use of anti-aircraft warfare after an Austrian plane was shot down with ground-to-air fire, as well as the first medical evacuation by the Serbian army. Upon mobilisation, in accordance with the Schlieffen Plan , 80% of the German Army was located on the Western Front, with the remainder acting as a screening force in the East. Rather than a direct attack across their shared frontier,
20460-636: The capital of the recently annexed Bosnia and Herzegovina . Cvjetko Popović , Gavrilo Princip , Nedeljko Čabrinović , Trifko Grabež , Vaso Čubrilović ( Bosnian Serbs ) and Muhamed Mehmedbašić (from the Bosniaks community), from the movement known as Young Bosnia , took up positions along the Archduke's motorcade route, to assassinate him. Supplied with arms by extremists within the Serbian Black Hand intelligence organisation, they hoped his death would free Bosnia from Austrian rule. Čabrinović threw
20646-416: The case of the T4 phage , the construction of new virus particles involves the assistance of helper proteins that act catalytically during phage morphogenesis . The base plates are assembled first, with the tails being built upon them afterward. The head capsids, constructed separately, will spontaneously assemble with the tails. During assembly of the phage T4 virion , the morphogenetic proteins encoded by
20832-544: The cell wall peptidoglycan . An altogether different phage type, the filamentous phage , makes the host cell continually secrete new virus particles. Released virions are described as free, and, unless defective, are capable of infecting a new bacterium. Budding is associated with certain Mycoplasma phages. In contrast to virion release, phages displaying a lysogenic cycle do not kill the host and instead become long-term residents as prophages . Research in 2017 revealed that
21018-466: The chance of a decisive outcome, while it had failed to achieve the primary objective of avoiding a long, two-front war. As was apparent to several German leaders, this amounted to a strategic defeat; shortly after the First Battle of the Marne , Crown Prince Wilhelm told an American reporter "We have lost the war. It will go on for a long time but lost it is already." On 30 August 1914, New Zealand occupied German Samoa (now Samoa ). On 11 September,
21204-458: The clinical futility of further treatment, an Emergency Investigational New Drug (eIND) was filed as a last effort to at the very least gain valuable medical data from the situation, and approved, so he was subjected to phage therapy using a percutaneously (PC) injected cocktail containing nine different phages that had been identified as effective against the primary infection strain by rapid isolation and testing techniques (a process which took under
21390-410: The contrast between viruses and the background, electron-dense "stains" are used. These are solutions of salts of heavy metals, such as tungsten , that scatter the electrons from regions covered with the stain. When virions are coated with stain (positive staining), fine detail is obscured. Negative staining overcomes this problem by staining the background only. A complete virus particle, known as
21576-426: The correct receptors when in solution, such as blood, lymphatic circulation, irrigation, soil water, etc. Myovirus bacteriophages use a hypodermic syringe -like motion to inject their genetic material into the cell. After contacting the appropriate receptor, the tail fibers flex to bring the base plate closer to the surface of the cell. This is known as reversible binding. Once attached completely, irreversible binding
21762-511: The cost of 199 submarines. World War I also saw the first use of aircraft carriers in combat, with HMS Furious launching Sopwith Camels in a successful raid against the Zeppelin hangars at Tondern in July 1918, as well as blimps for antisubmarine patrol. Faced with Russia in the east, Austria-Hungary could spare only one-third of its army to attack Serbia. After suffering heavy losses,
21948-513: The creation of new independent states, including Poland , Finland , the Baltic states , Czechoslovakia , and Yugoslavia . The League of Nations was established to maintain world peace, but its failure to manage instability during the interwar period contributed to the outbreak of World War II in 1939. Before World War II , the events of 1914–1918 were generally known as the Great War or simply
22134-449: The creation of strong defensive systems largely impervious to massed infantry advances, such as barbed wire , machine guns and above all far more powerful artillery , which dominated the battlefield and made crossing open ground extremely difficult. Both sides struggled to develop tactics for breaching entrenched positions without heavy casualties. In time, technology enabled the production of new offensive weapons, such as gas warfare and
22320-946: The crowds listened to music and drank wine, as if nothing had happened." Nevertheless, the impact of the murder of the heir to the throne was significant, and has been described by historian Christopher Clark as a "9/11 effect, a terrorist event charged with historic meaning, transforming the political chemistry in Vienna". Austro-Hungarian authorities encouraged subsequent anti-Serb riots in Sarajevo . Violent actions against ethnic Serbs were also organised outside Sarajevo, in other cities in Austro-Hungarian-controlled Bosnia and Herzegovina, Croatia and Slovenia. Austro-Hungarian authorities in Bosnia and Herzegovina imprisoned approximately 5,500 prominent Serbs, 700 to 2,200 of whom died in prison. A further 460 Serbs were sentenced to death. A predominantly Bosniak special militia known as
22506-463: The environment can cause cheese to not ferment. In order to avoid this, mixed-strain starter cultures and culture rotation regimes can be used. Genetic engineering of culture microbes – especially Lactococcus lactis and Streptococcus thermophilus – have been studied for genetic analysis and modification to improve phage resistance . This has especially focused on plasmid and recombinant chromosomal modifications. Some research has focused on
22692-671: The expansion of the French colonial empire . In 1873, Bismarck negotiated the League of the Three Emperors , which included Austria-Hungary , Russia and Germany. After the 1877–1878 Russo-Turkish War , the League was dissolved due to Austrian concerns over the expansion of Russian influence in the Balkans , an area they considered to be of vital strategic interest. Germany and Austria-Hungary then formed
22878-431: The extreme of the ssRNA virus case. Viruses undergo genetic change by several mechanisms. These include a process called antigenic drift where individual bases in the DNA or RNA mutate to other bases. Most of these point mutations are "silent"—they do not change the protein that the gene encodes—but others can confer evolutionary advantages such as resistance to antiviral drugs . Antigenic shift occurs when there
23064-446: The filtered, infectious substance a "virus" and this discovery is considered to be the beginning of virology. The subsequent discovery and partial characterization of bacteriophages by Frederick Twort and Félix d'Herelle further catalyzed the field, and by the early 20th century many viruses had been discovered. In 1926, Thomas Milton Rivers defined viruses as obligate parasites. Viruses were demonstrated to be particles, rather than
23250-400: The first time on the Western Front. Several types of gas soon became widely used by both sides and though it never proved a decisive, battle-winning weapon, it became one of the most feared and best-remembered horrors of the war. In February 1916, the Germans attacked French defensive positions at the Battle of Verdun , lasting until December 1916. Casualties were greater for the French, but
23436-399: The form of single-stranded nucleoprotein complexes, through pores called plasmodesmata . Bacteria, like plants, have strong cell walls that a virus must breach to infect the cell. Given that bacterial cell walls are much thinner than plant cell walls due to their much smaller size, some viruses have evolved mechanisms that inject their genome into the bacterial cell across the cell wall, while
23622-461: The former Soviet Republic of Georgia (pioneered there by Giorgi Eliava with help from the co-discoverer of bacteriophages, Félix d'Hérelle ) during the 1920s and 1930s for treating bacterial infections. D'Herelle "quickly learned that bacteriophages are found wherever bacteria thrive: in sewers, in rivers that catch waste runoff from pipes, and in the stools of convalescent patients." They had widespread use, including treatment of soldiers in
23808-586: The front. Serbian and French troops finally made a breakthrough in September 1918 in the Vardar offensive , after most German and Austro-Hungarian troops had been withdrawn. The Bulgarians were defeated at the Battle of Dobro Pole , and by 25 September British and French troops had crossed the border into Bulgaria proper as the Bulgarian army collapsed. Bulgaria capitulated four days later, on 29 September 1918. The German high command responded by despatching troops to hold
23994-414: The functions and interactions of the proteins employed in the machinery of DNA replication , repair and recombination , and on how viruses are assembled from protein and nucleic acid components (molecular morphogenesis ). Phages may be released via cell lysis, by extrusion, or, in a few cases, by budding. Lysis, by tailed phages, is achieved by an enzyme called endolysin , which attacks and breaks down
24180-425: The genes that are essential for growth of the bacteriophage under laboratory conditions. These studies were made possible by the availability of two classes of conditional lethal mutants . One class of such mutants was referred to as amber mutants . The other class of conditional lethal mutants was referred to as temperature-sensitive mutants Studies of these two classes of mutants led to considerable insight into
24366-526: The globe, some of which were subsequently used to attack Allied merchant shipping . These were systematically hunted down by the Royal Navy, though not before causing considerable damage. One of the most successful was the SMS ; Emden , part of the German East Asia Squadron stationed at Qingdao , which seized or sank 15 merchantmen, a Russian cruiser and a French destroyer. Most of the squadron
24552-534: The high ground, while their trenches tended to be better built; those constructed by the French and English were initially considered "temporary", only needed until an offensive would destroy the German defences. Both sides tried to break the stalemate using scientific and technological advances. On 22 April 1915, at the Second Battle of Ypres , the Germans (violating the Hague Convention ) used chlorine gas for
24738-488: The host bacterium while they are dormant by adding new functions to the bacterial genome , in a phenomenon called lysogenic conversion . Examples are the conversion of harmless strains of Corynebacterium diphtheriae or Vibrio cholerae by bacteriophages to highly virulent ones that cause diphtheria or cholera , respectively. Strategies to combat certain bacterial infections by targeting these toxin-encoding prophages have been proposed. Bacterial cells are protected by
24924-406: The host. At some point, the provirus or prophage may give rise to the active virus, which may lyse the host cells. Enveloped viruses (e.g., HIV) typically are released from the host cell by budding . During this process, the virus acquires its envelope, which is a modified piece of the host's plasma or other, internal membrane. The genetic material within virus particles, and the method by which
25110-517: The infected cell. Cells in which the virus is latent and inactive show few signs of infection and often function normally. This causes persistent infections and the virus is often dormant for many months or years. This is often the case with herpes viruses . Viruses are by far the most abundant biological entities on Earth and they outnumber all the others put together. They infect all types of cellular life including animals, plants, bacteria and fungi . Different types of viruses can infect only
25296-452: The infection was more pervasive than originally thought. Once on the combination of the IV and PC therapy the patient's downward clinical trajectory reversed, and within two days he had awoken from his coma and become responsive. As his immune system began to function he had to be temporarily removed from the cocktail because his fever was spiking to over 104 °F (40 °C), but after two days
25482-467: The investigation and trial of Serbians linked to the assassination. Claiming this amounted to rejection, Austria broke off diplomatic relations and ordered partial mobilisation the next day; on 28 July, they declared war on Serbia and began shelling Belgrade . Russia ordered general mobilization in support of Serbia on 30 July. Anxious to ensure backing from the SPD political opposition by presenting Russia as
25668-423: The ion emission and its dynamics during phage infection and offers high specificity and speed for detection. Phage display is a different use of phages involving a library of phages with a variable peptide linked to a surface protein. Each phage genome encodes the variant of the protein displayed on its surface (hence the name), providing a link between the peptide variant and its encoding gene. Variant phages from
25854-567: The leg in human patients. The FDA approved the study as a Phase I clinical trial. The study's results demonstrated the safety of therapeutic application of bacteriophages, but did not show efficacy. The authors explained that the use of certain chemicals that are part of standard wound care (e.g. lactoferrin or silver) may have interfered with bacteriophage viability. Shortly after that, another controlled clinical trial in Western Europe (treatment of ear infections caused by Pseudomonas aeruginosa )
26040-732: The library may be selected through their binding affinity to an immobilized molecule (e.g., botulism toxin) to neutralize it. The bound, selected phages can be multiplied by reinfecting a susceptible bacterial strain, thus allowing them to retrieve the peptides encoded in them for further study. Phage proteins often have antimicrobial activity and may serve as leads for peptidomimetics , i.e. drugs that mimic peptides. Phage-ligand technology makes use of phage proteins for various applications, such as binding of bacteria and bacterial components (e.g. endotoxin ) and lysis of bacteria. Bacteriophages are important model organisms for studying principles of evolution and ecology . Bacteriophages present in
26226-416: The material is replicated, varies considerably between different types of viruses. The range of structural and biochemical effects that viruses have on the host cell is extensive. These are called ' cytopathic effects '. Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis, alterations to the cell's surface membrane and apoptosis . Often cell death
26412-416: The most numerous type of biological entity. Since Dmitri Ivanovsky 's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology , a subspeciality of microbiology . When infected,
26598-460: The ocean, even to neutral ships. Since there was limited response to this tactic, Germany expected a similar response to its unrestricted submarine warfare. The Battle of Jutland in May/June 1916 was the only full-scale clash of battleships during the war, and one of the largest in history. The clash was indecisive, though the Germans inflicted more damage than they received; thereafter the bulk of
26784-553: The original phage cocktails, but they were continued because they seemed to be preventing minocycline resistance from developing in the bacterial samples collected so were having a useful synergistic effect. Phages have increasingly been used to safen food products and to forestall spoilage bacteria . Since 2006, the United States Food and Drug Administration (FDA) and United States Department of Agriculture (USDA) have approved several bacteriophage products. LMP-102 (Intralytix)
26970-461: The original virus. Their life cycle differs greatly between species, but there are six basic stages in their life cycle: Attachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range and type of host cell of a virus. For example, HIV infects a limited range of human leucocytes . This is because its surface protein, gp120 , specifically interacts with
27156-423: The other hand, phages of Inoviridae have been shown to complicate biofilms involved in pneumonia and cystic fibrosis and to shelter the bacteria from drugs meant to eradicate disease, thus promoting persistent infection. Meanwhile, bacteriophage researchers have been developing engineered viruses to overcome antibiotic resistance , and engineering the phage genes responsible for coding enzymes that degrade
27342-446: The phage genes interact with each other in a characteristic sequence. Maintaining an appropriate balance in the amounts of each of these proteins produced during viral infection appears to be critical for normal phage T4 morphogenesis . The DNA is packed efficiently within the heads. The whole process takes about 15 minutes. Early studies of bactioriophage T4 (1962-1964) provided an opportunity to gain understanding of virtually all of
27528-436: The phage cocktail showed a 2.3-fold higher survival rate compared to those untreated at seven days post-infection. In 2017, a 68-year-old diabetic patient with necrotizing pancreatitis complicated by a pseudocyst infected with MDR A. baumannii strains was being treated with a cocktail of Azithromycin, Rifampicin, and Colistin for 4 months without results and overall rapidly declining health. Because discussion had begun of
27714-442: The phage cocktails were re-introduced at levels he was able to tolerate. The original three-antibiotic cocktail was replaced by minocycline after the bacterial strain was found not to be resistant to this and he rapidly regained full lucidity, although he was not discharged from the hospital until roughly 145 days after phage therapy began. Towards the end of the therapy it was discovered that the bacteria had become resistant to both of
27900-399: The phage's host range. Polysaccharide-degrading enzymes are virion-associated proteins that enzymatically degrade the capsular outer layer of their hosts at the initial step of a tightly programmed phage infection process. Host growth conditions also influence the ability of the phage to attach and invade them. As phage virions do not move independently, they must rely on random encounters with
28086-416: The polymerase during genome replication. This process appears to be an adaptation for coping with genome damage. Viral populations do not grow through cell division, because they are acellular. Instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell. When infected, the host cell is forced to rapidly produce thousands of copies of
28272-438: The potential of bacteriophages as antimicrobial against foodborne pathogens and biofilm formation within the dairy industry. As the spread of antibiotic resistance is a main concern within the dairy industry, phages can serve as a promising alternative. The life cycle of bacteriophages tends to be either a lytic cycle or a lysogenic cycle . In addition, some phages display pseudolysogenic behaviors. With lytic phages such as
28458-474: The presence of pathogenic viruses such as rotavirus, norovirus, and HAV. Research conducted on wastewater treatment systems has revealed significant disparities in the behavior of coliphages compared to fecal coliforms, demonstrating a distinct correlation with the recovery of pathogenic viruses at the treatment's conclusion. Establishing a secure discharge threshold, studies have determined that discharges below 3000 PFU/100 mL are considered safe in terms of limiting
28644-789: The protection of the " cruiser rules ", which demanded warning and movement of crews to "a place of safety" (a standard that lifeboats did not meet). Finally, in early 1917, Germany adopted a policy of unrestricted submarine warfare , realising the Americans would eventually enter the war. Germany sought to strangle Allied sea lanes before the United States could transport a large army overseas, but, after initial successes, eventually failed to do so. The U-boat threat lessened in 1917, when merchant ships began travelling in convoys , escorted by destroyers . This tactic made it difficult for U-boats to find targets, which significantly lessened losses; after
28830-960: The ranks of subrealm, subkingdom, and subclass are unused, whereas all other ranks are in use. The Nobel Prize-winning biologist David Baltimore devised the Baltimore classification system. The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification. The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. Viral genomes may be single-stranded (ss) or double-stranded (ds), RNA or DNA, and may or may not use reverse transcriptase (RT). In addition, ssRNA viruses may be either sense (+) or antisense (−). This classification places viruses into seven groups: Examples of common human diseases caused by viruses include
29016-422: The regressive hypothesis did not explain why even the smallest of cellular parasites do not resemble viruses in any way. The escape hypothesis did not explain the complex capsids and other structures on virus particles. The virus-first hypothesis contravened the definition of viruses in that they require host cells. Viruses are now recognised as ancient and as having origins that pre-date the divergence of life into
29202-519: The release of pathogenic viruses. In 2011, the FDA cleared the first bacteriophage-based product for in vitro diagnostic use. The KeyPath MRSA/MSSA Blood Culture Test uses a cocktail of bacteriophage to detect Staphylococcus aureus in positive blood cultures and determine methicillin resistance or susceptibility. The test returns results in about five hours, compared to two to three days for standard microbial identification and susceptibility test methods. It
29388-479: The result of spread to an animal or human host where the virus had not been identified before. It can be an emergent virus , one that represents a new virus, but it can also be an extant virus that has not been previously identified . The SARS-CoV-2 coronavirus that caused the COVID-19 pandemic is an example of a novel virus. Classification seeks to describe the diversity of viruses by naming and grouping them on
29574-529: The result of repeated instances of site-specific recombination and illegitimate recombination (the result of phage genome acquisition of bacterial host genetic sequences). Evolutionary mechanisms shaping the genomes of bacterial viruses vary between different families and depend upon the type of the nucleic acid, characteristics of the virion structure, as well as the mode of the viral life cycle. Some marine roseobacter phages contain deoxyuridine (dU) instead of deoxythymidine (dT) in their genomic DNA. There
29760-451: The same virion for the virus to be infectious, as demonstrated by brome mosaic virus and several other plant viruses. A viral genome, irrespective of nucleic acid type, is almost always either single-stranded (ss) or double-stranded (ds). Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of two complementary paired nucleic acids, analogous to
29946-408: The significance of many of these interactions remains unclear, but these studies suggest that there most likely are several key interactions and many indirect interactions whose role remains uncharacterized. Bacteriophages are a major threat to bacteria and prokaryotes have evolved numerous mechanisms to block infection or to block the replication of bacteriophages within host cells. The CRISPR system
30132-522: The size and shape of the capsid varies along with the size of the genome. The largest bacteriophage genomes reach a size of 735 kb. Bacteriophage genomes can be highly mosaic , i.e. the genome of many phage species appear to be composed of numerous individual modules. These modules may be found in other phage species in different arrangements. Mycobacteriophages , bacteriophages with mycobacterial hosts, have provided excellent examples of this mosaicism. In these mycobacteriophages, genetic assortment may be
30318-644: The spread of bacterial disease. Other applications for bacteriophages are as biocides for environmental surfaces, e.g., in hospitals, and as preventative treatments for catheters and medical devices before use in clinical settings. The technology for phages to be applied to dry surfaces, e.g., uniforms, curtains, or even sutures for surgery now exists. Clinical trials reported in Clinical Otolaryngology show success in veterinary treatment of pet dogs with otitis . The sensing of phage-triggered ion cascades (SEPTIC) bacterium sensing and identification method uses
30504-399: The structure-mediated self-assembly of the virus particles, some modification of the proteins often occurs. In viruses such as HIV, this modification (sometimes called maturation) occurs after the virus has been released from the host cell. Release – Viruses can be released from the host cell by lysis , a process that kills the cell by bursting its membrane and cell wall if present: this
30690-457: The study of the origin of life , as it lends further credence to the hypothesis that life could have started as self-assembling organic molecules . The virocell model first proposed by Patrick Forterre considers the infected cell to be the "living form" of viruses and that virus particles (virions) are analogous to spores . Although the living versus non-living debate continues, the virocell model has gained some acceptance. Viruses display
30876-441: The temperate phage PaP3 changed the expression of 38% (2160/5633) of its host's genes. Many of these effects are probably indirect, hence the challenge becomes to identify the direct interactions among bacteria and phage. Several attempts have been made to map protein–protein interactions among phage and their host. For instance, bacteriophage lambda was found to interact with its host, E. coli , by dozens of interactions. Again,
31062-464: The term First World War was in September 1914 by German biologist and philosopher Ernst Haeckel who stated, "There is no doubt that the course and character of the feared 'European War' ... will become the first world war in the full sense of the word." For much of the 19th century, the major European powers maintained a tenuous balance of power , known as the Concert of Europe . After 1848, this
31248-682: The threat posed by the closing of this gap was more important than competing with the Royal Navy. After Germany expanded its standing army by 170,000 troops in 1913, France extended compulsory military service from two to three years; similar measures were taken by the Balkan powers and Italy, which led to increased expenditure by the Ottomans and Austria-Hungary. Absolute figures are difficult to calculate due to differences in categorising expenditure since they often omit civilian infrastructure projects like railways which had logistical importance and military use. It
31434-494: The unassigned genus Lilyvirus of the order Caudovirales containing a linear dsDNA genome. In 1896, Ernest Hanbury Hankin reported that something in the waters of the Ganges and Yamuna rivers in India had a marked antibacterial action against cholera and it could pass through a very fine porcelain filter. In 1915, British bacteriologist Frederick Twort , superintendent of
31620-446: The viral messenger RNA (mRNA). Positive-sense viral RNA is in the same sense as viral mRNA and thus at least a part of it can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. DNA nomenclature for viruses with genomic ssDNA is similar to RNA nomenclature, in that positive-strand viral ssDNA
31806-824: The viral capsid remains outside. Uncoating is a process in which the viral capsid is removed: This may be by degradation by viral enzymes or host enzymes or by simple dissociation; the end-result is the releasing of the viral genomic nucleic acid. Replication of viruses involves primarily multiplication of the genome. Replication involves the synthesis of viral messenger RNA (mRNA) from "early" genes (with exceptions for positive-sense RNA viruses), viral protein synthesis , possible assembly of viral proteins, then viral genome replication mediated by early or regulatory protein expression. This may be followed, for complex viruses with larger genomes, by one or more further rounds of mRNA synthesis: "late" gene expression is, in general, of structural or virion proteins. Assembly – Following
31992-503: The virus to enter. Penetration or viral entry follows attachment: Virions enter the host cell through receptor-mediated endocytosis or membrane fusion . The infection of plant and fungal cells is different from that of animal cells. Plants have a rigid cell wall made of cellulose , and fungi one of chitin, so most viruses can get inside these cells only after trauma to the cell wall. Nearly all plant viruses (such as tobacco mosaic virus) can also move directly from cell to cell, in
32178-460: The virus useless or uncompetitive. To compensate, RNA viruses often have segmented genomes—the genome is split into smaller molecules—thus reducing the chance that an error in a single-component genome will incapacitate the entire genome. In contrast, DNA viruses generally have larger genomes because of the high fidelity of their replication enzymes. Single-strand DNA viruses are an exception to this rule, as mutation rates for these genomes can approach
32364-577: The war ended with the Armistice of 11 November 1918 . The Paris Peace Conference of 1919–1920 imposed settlements on the defeated powers, most notably the Treaty of Versailles , by which Germany lost significant territories, was disarmed, and was required to pay large war reparations to the Allies. The dissolution of the Russian, German, Austro-Hungarian, and Ottoman Empires redrew national boundaries and resulted in
32550-581: The war involved British, French, and German colonial forces in Africa. On 6–7 August, French and British troops invaded the German protectorates of Togoland and Kamerun . On 10 August, German forces in South-West Africa attacked South Africa; sporadic and fierce fighting continued for the rest of the war. The German colonial forces in German East Africa , led by Colonel Paul von Lettow-Vorbeck , fought
32736-482: The water column of the world's oceans, and the second largest component of biomass after prokaryotes , where up to 9x10 virions per millilitre have been found in microbial mats at the surface, and up to 70% of marine bacteria may be infected by bacteriophages. Bacteriophages were used from the 1920s as an alternative to antibiotics in the former Soviet Union and Central Europe, as well as in France. They are seen as
32922-418: The west , which despite initial successes left the German Army exhausted and demoralised. A successful Allied counter-offensive from August 1918 caused a collapse of the German front line. By early November, Bulgaria, the Ottoman Empire and Austria-Hungary had each signed armistices with the Allies, leaving Germany isolated. Facing a revolution at home , Kaiser Wilhelm II abdicated on 9 November, and
33108-432: Was a major factor in the deadly Spanish flu pandemic. The causes of World War I included the rise of Germany and decline of the Ottoman Empire , which disturbed the long-standing balance of power in Europe, as well as economic competition between nations triggered by industrialisation and imperialism . Growing tensions between the great powers and in the Balkans reached a breaking point on 28 June 1914, when
33294-412: Was approved for treating ready-to-eat (RTE) poultry and meat products. In that same year, the FDA approved LISTEX (developed and produced by Micreos ) using bacteriophages on cheese to kill Listeria monocytogenes bacteria, in order to give them generally recognized as safe (GRAS) status. In July 2007, the same bacteriophage were approved for use on all food products. In 2011 USDA confirmed that LISTEX
33480-403: Was challenged by Britain's withdrawal into so-called splendid isolation , the decline of the Ottoman Empire , New Imperialism , and the rise of Prussia under Otto von Bismarck . Victory in the 1870–1871 Franco-Prussian War allowed Bismarck to consolidate a German Empire . Post-1871, the primary aim of French policy was to avenge this defeat, but by the early 1890s, this had switched to
33666-654: Was refused. Early on the morning of 4 August, the Germans invaded, and Albert I of Belgium called for assistance under the Treaty of London . Britain sent Germany an ultimatum demanding they withdraw from Belgium; when this expired at midnight, without a response, the two empires were at war. Germany promised to support Austria-Hungary's invasion of Serbia, but interpretations of what this meant differed. Previously tested deployment plans had been replaced early in 1914, but those had never been tested in exercises. Austro-Hungarian leaders believed Germany would cover its northern flank against Russia. Beginning on 12 August,
33852-496: Was reported in the journal Clinical Otolaryngology in August 2009. The study concludes that bacteriophage preparations were safe and effective for treatment of chronic ear infections in humans. Additionally, there have been numerous animal and other experimental clinical trials evaluating the efficacy of bacteriophages for various diseases, such as infected burns and wounds, and cystic fibrosis-associated lung infections, among others. On
34038-453: Was restored to good health by the bacteriophages. It was d'Hérelle who conducted much research into bacteriophages and introduced the concept of phage therapy . In 1919, in Paris, France, d'Hérelle conducted the first clinical application of a bacteriophage, with the first reported use in the United States being in 1922. In 1969, Max Delbrück , Alfred Hershey , and Salvador Luria were awarded
34224-659: Was returning to Germany when it sank two British armoured cruisers at the Battle of Coronel in November 1914, before being virtually destroyed at the Battle of the Falkland Islands in December. The SMS Dresden escaped with a few auxiliaries, but after the Battle of Más a Tierra , these too were either destroyed or interned. Soon after the outbreak of hostilities, Britain began a naval blockade of Germany . This proved effective in cutting off vital supplies, though it violated accepted international law. Britain also mined international waters which closed off entire sections of
34410-471: Was the first accelerated antibiotic-susceptibility test approved by the FDA. Government agencies in the West have for several years been looking to Georgia and the former Soviet Union for help with exploiting phages for counteracting bioweapons and toxins, such as anthrax and botulism . Developments are continuing among research groups in the U.S. Other uses include spray application in horticulture for protecting plants and vegetable produce from decay and
34596-759: Was the foundation of German foreign policy but in 1890, he was forced to retire by Wilhelm II . The latter was persuaded not to renew the Reinsurance Treaty by his new Chancellor , Leo von Caprivi . This gave France an opening to agree the Franco-Russian Alliance in 1894, which was then followed by the 1904 Entente Cordiale with Britain. The Triple Entente was completed by the 1907 Anglo-Russian Convention . While not formal alliances, by settling long-standing colonial disputes in Asia and Africa, British support for France or Russia in any future conflict became
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