E2F is a group of genes that encodes a family of transcription factors (TF) in higher eukaryotes . Three of them are activators : E2F1, 2 and E2F3a. Six others act as repressors : E2F3b, E2F4-8. All of them are involved in the cell cycle regulation and synthesis of DNA in mammalian cells. E2Fs as TFs bind to the TTTCCCGC (or slight variations of this sequence) consensus binding site in the target promoter sequence.
69-444: Schematic diagram of the amino acid sequences of E2F family members ( N-terminus to the left, C-terminus to the right) highlighting the relative locations of functional domains within each member: Homo sapiens E2F1 mRNA or E2F1 protein sequences from NCBI protein and nucleotide database. X-ray crystallographic analysis has shown that the E2F family of transcription factors has
138-643: A Science article reported that China had approved CanSino 's Ebola vaccine based on an Ad5 vector. It was tested in Sierra Leone , which had high HIV prevalence , making it more likely for such problems to be detected. CanSino's CEO said "we haven't seen anything with the Ebola vaccine" and speculated that HIV susceptibility might be limited to Ad5 vaccines which produced HIV proteins. In research reported in The Lancet in May,
207-540: A fold similar to the winged-helix DNA-binding motif . E2F family members play a major role during the G1/S transition in mammalian and plant cell cycle (see KEGG cell cycle pathway ). DNA microarray analysis reveals unique sets of target promoters among E2F family members suggesting that each protein has a unique role in the cell cycle. Among E2F transcriptional targets are cyclins , CDKs , checkpoints regulators, DNA repair and replication proteins. Nonetheless, there
276-594: A broad range of vertebrate hosts; in humans, more than 50 distinct adenoviral serotypes have been found to cause a wide range of illnesses , from mild respiratory infections in young children (known as the common cold ) to life-threatening multi-organ disease in people with a weakened immune system . This family contains the following genera : In humans, currently there are 88 human adenoviruses (HAdVs) in seven species (Human adenovirus A to G): Different types/serotypes are associated with different conditions: All these types are called Human mastadenovirus A–G by
345-426: A decade, was shipped to basic training sites on 18 October 2011. Prevention of adenovirus, as well as other respiratory illnesses, involves frequent hand washing for more than 20 seconds, avoiding touching the eyes, face, and nose with unwashed hands, and avoiding close contact with people with symptomatic adenovirus infection. Those with symptomatic adenovirus infection are additionally advised to cough or sneeze into
414-478: A hydroxyoxazolidine (Ser/Thr) or hydroxythiazolidine (Cys) intermediate]. This intermediate tends to revert to the amide form, expelling the attacking group, since the amide form is usually favored by free energy, (presumably due to the strong resonance stabilization of the peptide group). However, additional molecular interactions may render the amide form less stable; the amino group is expelled instead, resulting in an ester (Ser/Thr) or thioester (Cys) bond in place of
483-454: A linear dsDNA genome and are able to replicate in the nucleus of vertebrate cells using the host's replication machinery. Entry of adenoviruses into the host cell involves two sets of interactions between the virus and the host cell. Most of the action occurs at the vertices. Entry into the host cell is initiated by the knob domain of the fiber protein binding to the cell receptor. The two currently established receptors are: CD46 for
552-423: A major effort is made to limit hepatotoxicity and prevent multiple organ failure. Adenovirus dodecahedron can qualify as a potent delivery platform for foreign antigens to human myeloid dendritic cells (MDC), and that it is efficiently presented by MDC to M1-specific CD8+ T lymphocytes. A safety issue with adenoviruses is that they can cause an immune response with a related inflammatory response as occurred in
621-432: A potentially fatal disease involving vasculitis and hepatitis . Type 1 infection can also cause respiratory and eye infections. CAdV-1 also affects foxes ( Vulpes vulpes and Vulpes lagopus ) and may cause hepatitis and encephalitis. Canine adenovirus 2 (CAdV-2) is one of the potential causes of kennel cough . Core vaccines for dogs include attenuated live CAdV-2, which produces immunity to CAdV-1 and CAdV-2. CAdV-1
690-415: A primary structure, although the usage is not standard. The primary structure of a biological polymer to a large extent determines the three-dimensional shape ( tertiary structure ). Protein sequence can be used to predict local features , such as segments of secondary structure, or trans-membrane regions. However, the complexity of protein folding currently prohibits predicting the tertiary structure of
759-494: A protein from its sequence alone. Knowing the structure of a similar homologous sequence (for example a member of the same protein family ) allows highly accurate prediction of the tertiary structure by homology modeling . If the full-length protein sequence is available, it is possible to estimate its general biophysical properties , such as its isoelectric point . Sequence families are often determined by sequence clustering , and structural genomics projects aim to produce
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#1732852798453828-608: A second DNA binding site, increasing E2F binding stability. Most E2F have a pocket protein binding domain. Pocket proteins such as pRB and related proteins p107 and p130, can bind to E2F when hypophosphorylated. In activators, E2F binding with pRB has been shown to mask the transactivation domain responsible for transcription activation. In repressors E2F4 and E2F5, pocket protein binding (more often p107 and p130 than pRB) mediates recruitment of repression complexes to silence target genes. E2F6, E2F7, and E2F8 do not have pocket protein binding sites and their mechanism for gene silencing
897-444: A set of representative structures to cover the sequence space of possible non-redundant sequences. Adenovirus Adenoviruses (members of the family Adenoviridae ) are medium-sized (90–100 nm ), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953. They have
966-419: A vehicle to administer targeted therapy , in the form of recombinant DNA or protein. This therapy has been found especially useful in treating monogenic disease (e.g. cystic fibrosis , X-linked SCID , alpha1-antitrypsin deficiency) and cancer. In China, oncolytic adenovirus is an approved cancer treatment. Specific modifications on fiber proteins are used to target Adenovirus to certain cell types;
1035-550: A wide range of responses, from no symptoms at all to the severe infections typical of Adenovirus serotype 14 . Bat adenovirus TJM (Bt-AdV-TJM) is a novel species of the Mastadenovirus genus isolated from Myotis and Scotophilus kuhlii in China. It is most closely related to the tree shrew and canine AdVs. Two types of canine adenoviruses are well known, type 1 and 2. Type 1 (CAdV-1) causes infectious canine hepatitis ,
1104-651: Is a great deal of redundancy among the family members. Mouse embryos lacking E2F1, E2F2, and one of the E2F3 isoforms, can develop normally when either E2F3a or E2F3b, is expressed. The E2F family is generally split by function into two groups: transcription activators and repressors. Activators such as E2F1, E2F2, E2F3a promote and help carryout the cell cycle, while repressors inhibit the cell cycle. Yet, both sets of E2F have similar domains. E2F1-6 have DP1,2 heterodimerization domain which allows them to bind to DP1 or DP2, proteins distantly related to E2F. Binding with DP1,2 provides
1173-564: Is found to be present, it may not be the cause of any symptoms. Some immunocompromised individuals can shed the virus for weeks and show no symptoms. Most infections with adenovirus result in infections of the upper respiratory tract. Adenovirus infections often present as conjunctivitis , tonsillitis (which may look exactly like strep throat and cannot be distinguished from strep except by throat culture), an ear infection , or croup . Adenoviruses types 40 and 41 can also cause gastroenteritis . A combination of conjunctivitis and tonsillitis
1242-413: Is harder because of the reverse information loss (from amino acids to DNA sequence). The current lossless data compressor that provides higher compression is AC2. AC2 mixes various context models using Neural Networks and encodes the data using arithmetic encoding. The proposal that proteins were linear chains of α-amino acids was made nearly simultaneously by two scientists at the same conference in 1902,
1311-571: Is in transcriptional repressive complexes with the pocket proteins. pRb is one of the targets of the oncogenic human papilloma virus protein E7, and human adenovirus protein E1A. By binding to pRB, they stop the regulation of E2F transcription factors and drive the cell cycle to enable virus genome replication. Activators are maximally expressed late in G1 and can be found in association with E2F regulated promoters during
1380-419: Is innovative because an Ad26 based vaccine is used on the first day and an Ad5 vaccine is used on day 21. Another one is ChAd-SARS-CoV-2-S ; the vaccine reportedly prevented mice that were genetically modified to have human ACE2 (hACE2) receptors, presumably receptors that allow virus-entry into the cells, from being infected with SARS-CoV-2. Possible issues with using Adenovirus as vaccine vectors include:
1449-511: Is largely directed at the symptoms (such as acetaminophen for fever). The antiviral drug cidofovir has helped certain of those patients who had severe cases of illness; the number helped and to what degree, and the particular complications or symptoms it helped with, and when and where this happened, were not given in the source. A doctor may give antibiotic eyedrops for conjunctivitis, while awaiting results of bacterial cultures, and to help prevent secondary bacterial infections. Currently, there
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#17328527984531518-494: Is no adenovirus vaccine available to the general public, but a vaccine is available for the United States military for Types 4 and 7. Adenoviruses have long been a popular viral vector for gene therapy due to their ability to affect both replicating and non-replicating cells, accommodate large transgenes , and code for proteins without integrating genetic material into the host cell genome. More specifically, they are used as
1587-454: Is only expressed in terminally differentiated cells in mice. The balance between repressor and activator E2F regulate cell cycle progression. When activator E2F family proteins are knocked out, repressors become active to inhibit E2F target genes. The Rb tumor suppressor protein (pRb) binds to the E2F1 transcription factor preventing it from interacting with the cell's transcription machinery. In
1656-412: Is particularly common with adenovirus infections. Some children (especially the youngest) can develop adenovirus bronchiolitis or pneumonia , both of which can be severe. In babies, adenoviruses can also cause coughing fits that look almost exactly like whooping cough . Adenoviruses can also cause viral meningitis or encephalitis . Rarely, adenovirus can cause hemorrhagic cystitis (inflammation of
1725-463: Is separated by the DNA replication process into two phases: an early and a late phase. In both phases, a primary transcript that is alternatively spliced to generate monocistronic mRNAs compatible with the host's ribosome is generated, allowing for the products to be translated . The early genes are responsible for expressing mainly non-structural, regulatory proteins . The goal of these proteins
1794-495: Is significantly larger than other viruses in its Baltimore group , it is still a very simple virus and is heavily reliant on the host cell for survival and replication. The genes of adenoviruses can generally be divided into well-conserved sets of transcription units with six early transcription units (E1A, E1B, E2A, E2B, E3 and E4) and one late transcription unit ranging from L1-L5. In addition, adenoviruses also contain two intermediate transcription units named XI and IVa2. To increase
1863-462: Is subsequently released, which can enter the nucleus via the nuclear pore . After this the DNA associates with histone molecules already present in the nucleus, which allows it to interact with the host cell transcription machinery. Then, viral gene expression can occur, without integrating the viral genome into host cell chromosomes, and new virus particles can be generated. The adenovirus life cycle
1932-658: Is threefold: to alter the expression of host proteins that are necessary for DNA synthesis ; to activate other virus genes (such as the virus-encoded DNA polymerase ); and to avoid premature death of the infected cell by the host-immune defenses (blockage of apoptosis , blockage of interferon activity, and blockage of MHC class I translocation and expression). Some adenoviruses under specialized conditions can transform cells using their early gene products. E1A (binds Retinoblastoma tumor suppressor protein ) has been found to immortalize primary cells in vitro allowing E1B (binds p53 tumor suppressor) to assist and stably transform
2001-582: Is unclear. Cdk4(6)/cyclin D and cdk2/cyclin E phosphorylate pRB and related pocket proteins allowing them to disassociate from E2F. Activator E2F proteins can then transcribe S phase promoting genes. In REF52 cells, overexpression of activator E2F1 is able to push quiescent cells into S phase. While repressors E2F4 and 5 do not alter cell proliferation, they mediate G1 arrest. E2F activator levels are cyclic, with maximal expression during G1/S. In contrast, E2F repressors stay constant, especially since they are often expressed in quiescent cells. Specifically, E2F5
2070-434: The cyclol hypothesis advanced by Dorothy Wrinch , proposed that the linear polypeptide underwent a chemical cyclol rearrangement C=O + HN → {\displaystyle \rightarrow } C(OH)-N that crosslinked its backbone amide groups, forming a two-dimensional fabric . Other primary structures of proteins were proposed by various researchers, such as the diketopiperazine model of Emil Abderhalden and
2139-463: The host cell via the receptor on its surface. In 2010, the structure of the human adenovirus was solved at the atomic level, making it the largest high-resolution model ever. The virus is composed of around 1 million amino acid residues and weighs around 150 MDa . The adenovirus genome is linear, non-segmented double-stranded (ds) DNA that is between 26 and 48 k bp . This allows the virus to theoretically carry 22 to 40 genes . Although this
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2208-462: The ICTV , because all are members of the genus Mastadenovirus . Adenoviruses are medium-sized (90–100 nm). The virions are composed of one linear piece of double-stranded DNA inside an icosahedral capsid . 240 hexon proteins make up the bulk of the capsid, while twelve penton bases cap the icosahedron's corners. The penton bases are associated with protruding fibers that aid in attachment to
2277-406: The active site of the protein, inhibiting its function. The protein is activated by cleaving off the inhibitory peptide. Some proteins even have the power to cleave themselves. Typically, the hydroxyl group of a serine (rarely, threonine) or the thiol group of a cysteine residue will attack the carbonyl carbon of the preceding peptide bond, forming a tetrahedrally bonded intermediate [classified as
2346-516: The amino -terminal end through to the carboxyl -terminal end. Either a three letter code or single letter code can be used to represent the 22 naturally encoded amino acids, as well as mixtures or ambiguous amino acids (similar to nucleic acid notation ). Peptides can be directly sequenced , or inferred from DNA sequences . Large sequence databases now exist that collate known protein sequences. In general, polypeptides are unbranched polymers, so their primary structure can often be specified by
2415-509: The encoded 22, and may be cyclised, modified and cross-linked. Peptides can be synthesised chemically via a range of laboratory methods. Chemical methods typically synthesise peptides in the opposite order (starting at the C-terminus) to biological protein synthesis (starting at the N-terminus). Protein sequence is typically notated as a string of letters, listing the amino acids starting at
2484-575: The protein has been synthesized on the ribosome , typically occurring in the endoplasmic reticulum , a subcellular organelle of the eukaryotic cell. Many other chemical reactions (e.g., cyanylation) have been applied to proteins by chemists, although they are not found in biological systems. In addition to those listed above, the most important modification of primary structure is peptide cleavage (by chemical hydrolysis or by proteases ). Proteins are often synthesized in an inactive precursor form; typically, an N-terminal or C-terminal segment blocks
2553-405: The pyrrol/piperidine model of Troensegaard in 1942. Although never given much credence, these alternative models were finally disproved when Frederick Sanger successfully sequenced insulin and by the crystallographic determination of myoglobin and hemoglobin by Max Perutz and John Kendrew . Any linear-chain heteropolymer can be said to have a "primary structure" by analogy to the usage of
2622-648: The 'vector' to transport the surface protein gene of SARS-CoV-2". The goal is to genetically express the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ). A replication-deficient chimpanzee adenovirus vaccine vector (ChAdOx1) is used by the Oxford–AstraZeneca COVID-19 vaccine that has been approved for use. The Janssen COVID-19 vaccine uses modified recombinant adenovirus type-26 (Ad26). Recombinant adenovirus type-5 (Ad5) are being used by Ad5-nCoV , ImmunityBio and UQ-CSL V451 . The Gam-COVID-Vac (aka Sputnik-V) product
2691-528: The 1920s when he argued that rubber was composed of macromolecules . Thus, several alternative hypotheses arose. The colloidal protein hypothesis stated that proteins were colloidal assemblies of smaller molecules. This hypothesis was disproved in the 1920s by ultracentrifugation measurements by Theodor Svedberg that showed that proteins had a well-defined, reproducible molecular weight and by electrophoretic measurements by Arne Tiselius that indicated that proteins were single molecules. A second hypothesis,
2760-513: The 74th meeting of the Society of German Scientists and Physicians, held in Karlsbad. Franz Hofmeister made the proposal in the morning, based on his observations of the biuret reaction in proteins. Hofmeister was followed a few hours later by Emil Fischer , who had amassed a wealth of chemical details supporting the peptide-bond model. For completeness, the proposal that proteins contained amide linkages
2829-694: The G1/S transition. The activation of E2F-3a genes follows upon the growth factor stimulation and the subsequent phosphorylation of the E2F inhibitor retinoblastoma protein, pRB . The phosphorylation of pRB is initiated by cyclin D / cdk4 , cdk6 complex and continued by cyclin E/cdk2. Cyclin D/cdk4,6 itself is activated by the MAPK signaling pathway . When bound to E2F-3a, pRb can directly repress E2F-3a target genes by recruiting chromatin remodeling complexes and histone modifying activities (e.g. histone deacetylase, HDAC ) to
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2898-699: The absence of pRb, E2F1 (along with its binding partner DP1) mediates the trans-activation of E2F1 target genes that facilitate the G1/S transition and S-phase. E2F targets genes that encode proteins involved in DNA replication (for example DNA polymerase , thymidine kinase , dihydrofolate reductase and cdc6 ), and chromosomal replication (replication origin-binding protein HsOrc1 and MCM5 ). When cells are not proliferating, E2F DNA binding sites contribute to transcriptional repression. In vivo footprinting experiments obtained on Cdc2 and B-myb promoters demonstrated E2F DNA binding site occupation during G0 and early G1, when E2F
2967-455: The adenovirus genome can occur. A terminal protein that is covalently bound to the 5' end of the adenovirus genome acts as a primer for replication. The viral DNA polymerase then uses a strand displacement mechanism, as opposed to the conventional Okazaki fragments used in mammalian DNA replication, to replicate the genome. The late phase of the adenovirus lifecycle is focused on producing sufficient quantities of structural protein to pack all
3036-423: The adenovirus. This co-receptor molecule is αV integrin . Binding to αV integrin results in endocytosis of the virus particle via clathrin-coated pits. Attachment to αV integrin stimulates cell signaling and thus induces actin polymerization, which facilitates clathrin-mediated endocytosis, and results in virion's entry into the host cell within an endosome . Once the virus has successfully gained entry into
3105-548: The arm or elbow instead of the hand, to avoid sharing cups and eating utensils, and to refrain from kissing others. Chlorination of swimming pools can prevent outbreaks of conjunctivitis caused by adenovirus. Diagnosis is from symptoms and history. Tests are only necessary in very serious cases. Tests include blood tests, eyes, nose or throat swabs, stool sample tests, and chest x-rays. In the laboratory, adenovirus can be identified with antigen detection, polymerase chain reaction (PCR), virus isolation and serology. Even if adenovirus
3174-469: The binding of protein VI to the endsomal membrane leading to a severe membrane curvature that ultimately disrupts the endosome. These changes, as well as the toxic nature of the pentons, destroy the endosome, resulting in the movement of the virion into the cytoplasm. With the help of cellular microtubules , the virus is transported to the nuclear pore complex, whereby the adenovirus particle disassembles. Viral DNA
3243-478: The body and water. Adenoviruses are spread primarily via respiratory droplets, however they can also be spread by fecal routes and via aerosols ( airborne transmission ). Research into the molecular mechanisms underlying adenoviral transmission provide empirical evidence in support of the hypothesis that coxsackievirus/adenovirus receptors (CARs) are needed to transport adenoviruses into certain naive/progenitor cell types. Humans infected with adenoviruses display
3312-420: The cells. Nevertheless, they are reliant upon each other to successfully transform the host cell and form tumors . E1A is mostly intrinsically disordered protein and contains CR3 domain which is critical for transcriptional activation. DNA replication separates the early and late phases. Once the early genes have liberated adequate virus proteins, replication machinery, and replication substrates, replication of
3381-666: The death of Jesse Gelsinger in 1999. To address this risk, the genome of the viral genes have been modified to remove some viral genes. One such modification is the gutless vector that removes almost all the viral genome. Adenovirus has been used for delivery of CRISPR/Cas9 gene editing systems, but high immune reactivity to viral infection has posed challenges in use for patients. Modified ( recombinant ) adenovirus vectors, including replication incompetent types, can deliver DNA coding for specific antigens . Adenovirus have been used to produce viral vector COVID-19 vaccines . "In four candidate COVID-19 vaccines... Ad5... serves as
3450-451: The general population or on people with weakened immune systems. In the past, US military recruits were vaccinated against two serotypes of adenovirus, with a corresponding decrease in illnesses caused by those serotypes. That vaccine is no longer manufactured. The U.S. Army Medical Research and Materiel Command announced on 31 October 2011 that a new adenovirus vaccine, which replaces the older version that has been out of production for over
3519-417: The genetic material produced by DNA replication. Once the viral components have successfully been replicated, the virus is assembled into its protein shells and released from the cell as a result of virally induced cell lysis . Adenovirus is capable of multiplicity reactivation (MR) (Yamamoto and Shimojo, 1971). MR is the process by which two, or more, virus genomes containing lethal damage interact within
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#17328527984533588-432: The group B human adenovirus serotypes and the coxsackievirus/adenovirus receptor (CAR) for all other serotypes. There are some reports suggesting MHC molecules and sialic acid residues functioning in this capacity as well. This is followed by a secondary interaction, where a motif in the penton base protein (see capsomere ) interacts with an integrin molecule. It is the co-receptor interaction that stimulates entry of
3657-404: The host cell, the endosome acidifies, which alters virus topology by causing capsid components to disband. The capsid is destabilized and protein VI, which is one of the capsid constituents (see Adenovirus genome ) is released from it. Protein VI contains an N-terminal amphiphatic alpha-helix, a helical domain that exhibits both hydrophobic and hydrophilic properties. This amphipathic helix enables
3726-465: The human body develops immunity to the vector itself, making subsequent booster shots difficult or impossible. In some cases, people have pre-existing immunity to Adenoviruses, making vector delivery ineffective. The use of Ad5 vaccines for COVID-19 worried researchers who had experience with two failed trials of an Ad5 vaccine, Phambili and STEP, due to the increased risk for uncircumcised male patients of contracting HIV-1 via unprotected anal sex. At
3795-561: The infected cell to form a viable virus genome. Such MR was demonstrated for adenovirus 12 after virions were irradiated with UV light and allowed to undergo multiple infection of host cells. In a review, numerous examples of MR in different viruses were described, and it was suggested that MR is a common form of sexual interaction that provides the survival advantage of recombinational repair of genome damages. Adenoviruses are unusually stable to chemical or physical agents and adverse pH conditions, allowing for prolonged survival outside of
3864-455: The laboratory. Protein primary structures can be directly sequenced , or inferred from DNA sequences . Amino acids are polymerised via peptide bonds to form a long backbone , with the different amino acid side chains protruding along it. In biological systems, proteins are produced during translation by a cell's ribosomes . Some organisms can also make short peptides by non-ribosomal peptide synthesis , which often use amino acids other than
3933-407: The peptide bond. This chemical reaction is called an N-O acyl shift . The ester/thioester bond can be resolved in several ways: The compression of amino acid sequences is a comparatively challenging task. The existing specialized amino acid sequence compressors are low compared with that of DNA sequence compressors, mainly because of the characteristics of the data. For example, modeling inversions
4002-401: The promoter. Peptide sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein . By convention, the primary structure of a protein is reported starting from the amino -terminal (N) end to the carboxyl -terminal (C) end. Protein biosynthesis is most commonly performed by ribosomes in cells. Peptides can also be synthesized in
4071-438: The protein can undergo a variety of post-translational modifications , which are briefly summarized here. The N-terminal amino group of a polypeptide can be modified covalently, e.g., The C-terminal carboxylate group of a polypeptide can also be modified, e.g., Finally, the peptide side chains can also be modified covalently, e.g., Most of the polypeptide modifications listed above occur post-translationally , i.e., after
4140-420: The sequence of amino acids along their backbone. However, proteins can become cross-linked, most commonly by disulfide bonds , and the primary structure also requires specifying the cross-linking atoms, e.g., specifying the cysteines involved in the protein's disulfide bonds. Other crosslinks include desmosine . The chiral centers of a polypeptide chain can undergo racemization . Although it does not change
4209-428: The sequence, it does affect the chemical properties of the sequence. In particular, the L -amino acids normally found in proteins can spontaneously isomerize at the C α {\displaystyle \mathrm {C^{\alpha }} } atom to form D -amino acids, which cannot be cleaved by most proteases . Additionally, proline can form stable trans-isomers at the peptide bond. Additionally,
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#17328527984534278-420: The term for proteins, but this usage is rare compared to the extremely common usage in reference to proteins. In RNA , which also has extensive secondary structure , the linear chain of bases is generally just referred to as the "sequence" as it is in DNA (which usually forms a linear double helix with little secondary structure). Other biological polymers such as polysaccharides can also be considered to have
4347-755: The time, it was concluded that heightened risk of HIV reception may be observed for any Ad5-based vector vaccine. In October 2020, these researchers wrote in The Lancet : "On the basis of these findings, we are concerned that use of an Ad5 vector for immunisation against SARS-CoV-2 could similarly increase the risk of HIV-1 acquisition among men who receive the vaccine." Vaccines using other technologies would not be affected, but Sputnik V , Convidecia and ImmunityBio's hAd5 would. Two studies found that Ad5-specific CD4 T cells are more susceptible to HIV infection than CD4 T cells specific to certain other vectors, such as Cytomegalovirus and Canarypox . By comparison,
4416-778: The urinary bladder—a form of urinary tract infection —with blood in the urine). Most people recover from adenovirus infections by themselves, but people with immunodeficiency sometimes die of adenovirus infections, and—rarely—even previously healthy people can die of these infections. This may be because sometimes adenoviral infection can lead to cardiac disorders. For example, in one study, some cardiac samples of patients with dilated cardiomyopathy were positive for presence of adenovirus type 8. Adenoviruses are often transmitted by expectoration (e.g. aerosols), but they can also be transmitted by contact with an infected person, or by virus particles left on objects such as towels and faucet handles. Some people with adenovirus gastroenteritis may shed
4485-444: The viral gene economy, adenoviruses accommodate genes on both strands of its dsDNA meaning that most of its genome is utilized for coding proteins. An interesting feature of this viral genome is that it has a terminal 55 kDa protein associated with each of the 5' ends of the linear dsDNA. These are used as primers in viral replication and ensure that the ends of the virus' linear genome are adequately replicated. Adenoviruses possess
4554-432: The virus in their stools for months after getting over the symptoms. The virus can be passed through water in swimming pools that are not sufficiently chlorinated. As with many other illnesses, good handwashing practice is one way to inhibit the person-to-person transmission of adenoviruses. Heat and bleach will kill adenoviruses on objects. There are no proven antiviral drugs to treat adenoviral infections, so treatment
4623-1233: Was initially used in a vaccine for dogs, but corneal edema was a common complication. Squirrel adenovirus (SqAdV) is reported to cause enteritis in red squirrels in Europe, while gray squirrels seem to be resistant. SqAdV is most closely related to the adenovirus of guinea pigs (GpAdV). Adenovirus in reptiles is poorly understood, but research is currently in progress. Adenoviruses are also known to cause respiratory infections in horses , cattle , pigs , sheep , and goats . Equine adenovirus 1 can also cause fatal disease in immunocompromised Arabian foals , involving pneumonia and destruction of pancreatic and salivary gland tissue. Tupaia adenovirus (TAV) (tree shrew adenovirus 1) has been isolated from tree shrews. Otarine adenovirus 1 has been isolated from sea lions ( Zalophus californianus ). The fowl adenoviruses are associated with many disease conditions in domestic fowl like inclusion body hepatitis , hydropericardium syndrome , Egg drop syndrome , Quail bronchitis , Gizzard erosions and many respiratory conditions. They have also been isolated from wild black kites (Milvus migrans). Titi monkey adenovirus
4692-428: Was isolated from a colony of monkeys. Currently there is a vaccine for adenovirus type 4 and 7 for US military personnel only. US military personnel are the recipients of this vaccine because they may be at a higher risk of infection. The vaccine contains a live virus, which may be shed in stool and lead to transmission. The vaccine is not approved for use outside of the military, as it has not been tested in studied in
4761-570: Was made as early as 1882 by the French chemist E. Grimaux. Despite these data and later evidence that proteolytically digested proteins yielded only oligopeptides, the idea that proteins were linear, unbranched polymers of amino acids was not accepted immediately. Some scientists such as William Astbury doubted that covalent bonds were strong enough to hold such long molecules together; they feared that thermal agitations would shake such long molecules asunder. Hermann Staudinger faced similar prejudices in
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