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62-411: Feline leukemia virus ( FeLV ) is a retrovirus that infects cats . FeLV can be transmitted from infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal's immune system , the virus weakens the cat's immune system, which can lead to diseases which can be lethal. Because FeLV is cat-to-cat contagious, FeLV+ cats should only live with other FeLV+ cats. FeLV

124-440: A " kissing stem-loop ". Although virions of different retroviruses do not have the same morphology or biology, all the virion components are very similar. The main virion components are: The retroviral genome is packaged as viral particles. These viral particles are dimers of single-stranded, positive-sense, linear RNA molecules. Retroviruses (and orterviruses in general) follow a layout of 5'– gag – pro – pol – env –3' in

186-405: A "test and elimination" regime, dramatically reducing the number of infected cats in the general population. The first vaccine became available in 1986. FeLV and feline immunodeficiency virus (FIV) are sometimes mistaken for one another, though the viruses differ in many ways. Although they are both in the same retroviral subfamily (Orthoretrovirinae), they are classified in different genera (FeLV

248-480: A cold or influenza . It has been associated with chemotherapy , radiation therapy , myelofibrosis , aplastic anemia (failure of white cell, red cell and platelet production), stem cell transplant, bone marrow transplant, HIV , AIDS , and steroid use. Other causes of low white blood cell count include systemic lupus erythematosus , Hodgkin's lymphoma , some types of cancer , typhoid , malaria , tuberculosis , dengue , rickettsial infections , enlargement of

310-461: A commonly prescribed antibiotic, is another drug known to cause leukopenia. There are also reports of leukopenia caused by divalproex sodium or valproic acid (Depakote), a drug used for epilepsy (seizures), mania (with bipolar disorder) and migraine. The anticonvulsant drug, lamotrigine , has been associated with a decrease in white blood cell count. The FDA monograph for metronidazole states that this medication can also cause leukopenia, and

372-453: A concern that insertional mutagenesis due to integration into the host genome might lead to cancer or leukemia. This is unlike Lentivirus , a genus of Retroviridae , which are able to integrate their RNA into the genome of non-dividing host cells. Two RNA genomes are packaged into each retrovirus particle, but, after an infection, each virus generates only one provirus . After infection, reverse transcription occurs and this process

434-689: A few months or may remain asymptomatic for longer; median survival time after diagnosis is 2.5 years. FeLV is categorized into four subgroups. The fatal diseases are leukemias , lymphomas , and non-regenerative anemias . Although there is no known cure for the virus infection, in 2006 the United States Department of Agriculture approved Lymphocyte T-Cell Immunomodulator as a treatment aid for FeLV (see Treatment ). In Canada, one feline infected with progressive Feline Leukemia Virus Type C and its Immune-Mediated Hemolytic Anemia complication has been successfully managed so far for over 6 months with

496-550: A high percentage of FeLV-Antigen negative lymphomas contain FeLV-DNA, indicating a "hit-and-run" mechanism of virus-induced tumor development. Once the virus has entered the cat, there are six stages to a FeLV infection: If the cat's immune system does not fight off the virus, then it progresses to: Cats infected with FeLV can serve as sources of infection of FeLV-A. Cats can pass the virus between themselves through saliva and close contact, by biting another cat, and (rarely) through

558-654: A litter box or food dish used by an infected cat. Once a cat has been infected with FeLV-A, additional mutated forms of the original FeLV-A virus may arise, as may FeLV subgroups B, C and T. In addition to domestic cats, some other members of Felidae are now threatened by FeLV (e.g. lynx and Florida panther ). Overwhelming epidemiologic evidence suggests FeLV is not transmissible to either humans or dogs. Approximately 0.5% of pet cats are persistently infected with FeLV, but many more pet cats (>35%) have specific IgG antibodies which indicate prior exposure and subsequent development of immunity instead of infection . FeLV

620-939: A newly introduced fish virus genus are retroviruses classified as complex. These viruses have genes called accessory genes, in addition to gag, pro, pol and env genes. Accessory genes are located between pol and env, downstream from the env, including the U3 region of LTR, or in the env and overlapping portions. While accessory genes have auxiliary roles, they also coordinate and regulate viral gene expression. In addition, some retroviruses may carry genes called oncogenes or onc genes from another class. Retroviruses with these genes (also called transforming viruses) are known for their ability to quickly cause tumors in animals and transform cells in culture into an oncogenic state. The polyproteins are cleaved into smaller proteins each with their own function. The nucleotides encoding them are known as subgenes . When retroviruses have integrated their own genome into

682-516: A nonadjuvanted canarypox virus-vectored recombinant infectious vaccine ( ATCvet code QI066AA01 and various combination vaccines), though no currently available vaccine offers 100% protection from the virus. Vaccination is recommended for high-risk cats: those that have access to the outdoors, feral cats, cats that do not have the virus but live with an infected cat, multicat households, and cats with an unknown status, such as cats in catteries and shelters. Serious side effects have also been reported as

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744-562: A positive result on this test. Other than ELISA and IFA testing, routine laboratory blood work may show changes that indicate infection but cannot be used as a definitive diagnosis. There may be blood cell count changes like leukopenia , decreased Packed Cell Volume (PCV) and Total Protein (TP) levels due to anemia , hemoconcentration and hypoglycemia due to vomiting and diarrhea, electrolyte imbalance caused by dehydration and anorexia, and recurrent urinary tract infections. Cats diagnosed as persistently infected by ELISA testing may die within

806-504: A result of FeLV vaccination; in particular, a small percentage of cats who received the adjuvanted killed virus vaccine developed vaccine-associated sarcomas , an aggressive tumour, at the injection site. The development of sarcomas with the use of the old FeLV and other vaccines may be due to the inflammation caused by aluminium adjuvants in the vaccines. Merial produces a recombinant vaccine consisting of canarypox virus carrying FeLV gag and env genes (sold as PUREVAX FeLV in

868-417: A subtype of leukopenia, refers to a decrease in the number of circulating neutrophil granulocytes , the most abundant white blood cells. The terms leukopenia and neutropenia may occasionally be used interchangeably, as the neutrophil count is the most important indicator of infection risk. Agranulocytosis is an acute form of neutropenia. Low white cell count may be due to acute viral infections, such as

930-445: A wide range of effects. The cat can fight off the infection and become totally immune, can become a healthy carrier that never gets sick itself but can infect other cats, or a mid-level case in which the cat has a compromised immune system. Nevertheless, the development of lymphomas is considered the final stage of the disease. Although it is thought that virus protein has to be present to induce lymphomas in cats, newer evidence shows that

992-401: Is neutropenia , the lowering of neutrophils (a specific type of white blood cell). Decreased white blood cell count may be present in cases of arsenic toxicity . Leukopenia can be identified with a complete blood count . Below are blood reference ranges for various types leucocytes/WBCs. The 2.5 percentile (right limits in intervals in image, showing 95% prediction intervals ) is

1054-575: Is a gamma-retrovirus and FIV is a lentivirus like HIV-1). Their shapes are quite different: FeLV is more circular while FIV is elongated. The two viruses are also quite different genetically, and their protein coats differ in size and composition. Although many of the diseases caused by FeLV and FIV are similar, the specific ways in which they are caused also differ. Also, while the feline leukemia virus may cause symptomatic illness in an infected cat, an FIV infected cat can remain completely asymptomatic its entire lifetime. Retrovirus A retrovirus

1116-483: Is a potent regulator of CD-4 lymphocyte production and function. It has been shown to increase lymphocyte numbers and Interleukin 2 production in animals. Lymphocyte T-Cell Immunomodulator is a single chain polypeptide . It is a strongly cationic glycoprotein , and is purified with cation exchange resin. Purification of protein from bovine-derived stromal cell supernatants produces a substantially homogeneous factor, free of extraneous materials. The bovine protein

1178-427: Is a retrovirus. This virus passes to newborn mice through mammary milk. When they are 6 months old, the mice carrying the virus get mammary cancer because of the retrovirus. In addition, leukemia virus I (HTLV-1), found in human T cell, has been found in humans for many years. It is estimated that this retrovirus causes leukemia in the ages of 40 and 50. It has a replicable structure that can induce cancer. In addition to

1240-493: Is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm , the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backward). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point

1302-450: Is accompanied by recombination . Recombination involves template strand switching between the two genome copies (copy choice recombination) during reverse transcription. From 5 to 14 recombination events per genome occur at each replication cycle. Genetic recombination appears to be necessary for maintaining genome integrity and as a repair mechanism for salvaging damaged genomes. The DNA formed after reverse transcription (the provirus)

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1364-430: Is added to a container or dish that contains the antibodies to the viral antigens. If the antigens are present in the sample, the antibodies will bind to them and an indicator on the test will change color. These give a definitive diagnosis, but it cannot differentiate between acute or persistent infections. Therefore, it is recommended that the cat be retested in three to four months after the positive result to determine if

1426-463: Is categorized into four subgroups, A, B, C and T. An infected cat has a combination of FeLV-A and one or more of the other subgroups. Symptoms, prognosis and treatment are all affected by subgroup. FeLV+ cats often have a shorter lifespan, but can still live "normal", healthy lives. The signs and symptoms of infection with feline leukemia virus are quite varied and include loss of appetite , poor coat condition, anisocoria (uneven pupils), infections of

1488-487: Is highly infectious. Kittens can be born with it, having contracted it from their mother while in utero . Infection is far higher in city cats, stray or owned, than in rural cats: this is entirely due to the amount of contact the cats have with each other. Testing for FeLV is possible with ELISA tests that look for viral antigens , free particles found in the bloodstream. These ELISA tests use blood samples most often, but can also use saliva or eye secretions. The sample

1550-506: Is homologous with other mammalian species and is a homogeneous 50 kDa glycoprotein with an isoelectric point of 6.5. The protein is prepared in a lyophilized 1 microgram dose. Reconstitution in sterile diluent produces a solution for subcutaneous injection. Interferon-ω (omega) is sold in Europe at least under the name Virbagen Omega and manufactured by Virbac. When used in treatment of cats infected with FeLV in non-terminal clinical stages (over

1612-429: Is intended as an aid in the treatment of cats infected with feline leukemia virus (FeLV) and/or feline immunodeficiency virus (FIV), and the associated symptoms of lymphocytopenia , opportunistic infection , anemia , granulocytopenia , or thrombocytopenia . The absence of any observed adverse events in several animal species suggests that the product has a very low toxicity profile. Lymphocyte T-Cell Immunomodulator

1674-500: Is longer than the RNA genome because each of the terminals have the U3 - R - U5 sequences called long terminal repeat (LTR). Thus, 5' terminal has the extra U3 sequence, while the other terminal has the U5 sequence. LTRs are able to send signals for vital tasks to be carried out such as initiation of RNA production or management of the rate of transcription. This way, LTRs can control replication, hence,

1736-509: Is now commonly used to describe a cancer-causing virus. This family now includes the following genera: Note that according to ICTV 2017, genus Spumavirus has been divided into five genera, and its former type species Simian foamy virus is now upgraded to genus Simiispumavirus with not less than 14 species, including new type species Eastern chimpanzee simian foamy virus . Both families in Group VII have DNA genomes contained within

1798-537: Is translated into molecules of the capsid protein, and for the pol gene; it is translated into molecules of reverse transcriptase. Retroviruses need a lot more of the Gag proteins than the Pol proteins and have developed advanced systems to synthesize the required amount of each. As an example, after Gag synthesis nearly 95 percent of the ribosomes terminate translation, while other ribosomes continue translation to synthesize Gag–Pol. In

1860-507: The Baltimore classification system, which groups viruses together based on their manner of messenger RNA synthesis, they are classified into two groups: Group VI: single-stranded RNA viruses with a DNA intermediate in their life cycle, and Group VII: double-stranded DNA viruses with an RNA intermediate in their life cycle. All members of Group VI use virally encoded reverse transcriptase , an RNA-dependent DNA polymerase, to produce DNA from

1922-427: The germ line , their genome is passed on to a following generation. These endogenous retroviruses (ERVs), contrasted with exogenous ones, now make up 5–8% of the human genome. Most insertions have no known function and are often referred to as " junk DNA ". However, many endogenous retroviruses play important roles in host biology, such as control of gene transcription, cell fusion during placental development in

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1984-501: The spleen , folate deficiencies, psittacosis , sepsis , Sjögren syndrome and Lyme disease . It has also been shown to be caused by deficiency in certain minerals , such as copper and zinc . Pseudoleukopenia can develop upon the onset of infection. The leukocytes (primarily neutrophils, responding to injury first) start migrating toward the site of infection, where they can be scanned. Their migration causes bone marrow to produce more WBCs to combat infection as well as to restore

2046-551: The HIV life cycle . Combination of several (typically three or four) antiretroviral drugs is known as highly active antiretroviral therapy (HAART). Feline leukemia virus and Feline immunodeficiency virus infections are treated with biologics , including the only immunomodulator currently licensed for sale in the United States, Lymphocyte T-Cell Immune Modulator (LTCI). Leukopenia Symptoms may include: Neutropenia ,

2108-482: The RNA genome. gag and pol encode polyproteins, each managing the capsid and replication. The pol region encodes enzymes necessary for viral replication, such as reverse transcriptase, protease and integrase. Depending on the virus, the genes may overlap or fuse into larger polyprotein chains. Some viruses contain additional genes. The lentivirus genus, the spumavirus genus, the HTLV / bovine leukemia virus (BLV) genus, and

2170-679: The RNA to DNA transcription processes used by retroviruses may have first caused DNA to be used as genetic material. In this model, the RNA world hypothesis , cellular organisms adopted the more chemically stable DNA when retroviruses evolved to create DNA from the RNA templates. An estimate of the date of evolution of the foamy-like endogenous retroviruses placed the time of the most recent common ancestor at > 450  million years ago . Gammaretroviral and lentiviral vectors for gene therapy have been developed that mediate stable genetic modification of treated cells by chromosomal integration of

2232-628: The US and Eurifel FeLV in Europe). This is thought to be safer than the old vaccine as it does not require an adjuvant to be effective. Although this is a live virus, it originates from a bird host and so does not replicate in mammals. Feline leukemia virus (FeLV ) is an RNA virus in the subfamily Oncovirinae belonging to the Retroviridae family. The virus comprises 5' and 3' LTRs and three genes: Gag (structural), Pol (enzymes) and Env (envelope and transmembrane);

2294-441: The age of 9 weeks) there have been substantial improvements in mortality rates; in non-anemic cats, mortality rate of 50% was reduced by approximately 20% following treatment. FeLV was first described in cats in 1964. The disease was originally associated with leukemia; however, it was later realized that the initial signs are generally anemia and immunosuppression . The first diagnostic test became available in 1973, which led to

2356-399: The course of the germination of an embryo , and resistance to exogenous retroviral infection. Endogenous retroviruses have also received special attention in the research of immunology -related pathologies, such as autoimmune diseases like multiple sclerosis , although endogenous retroviruses have not yet been proven to play any causal role in this class of disease. While transcription

2418-409: The disruption of cellular proto-oncogenes. Rous sarcoma virus contains the src gene that triggers tumor formation. Later it was found that a similar gene in cells is involved in cell signaling, which was most likely excised with the proviral DNA. Nontransforming viruses can randomly insert their DNA into proto-oncogenes, disrupting the expression of proteins that regulate the cell cycle. The promoter of

2480-419: The entire progress of the viral cycle. Although located in the nucleus, the non-integrated retroviral cDNA is a very weak substrate for transcription. For this reason, an integrated provirus is a necessary for permanent and an effective expression of retroviral genes. This DNA can be incorporated into host genome as a provirus that can be passed on to progeny cells. The retrovirus DNA is inserted at random into

2542-471: The established knowledge on this topic. However, although later research disproved some of the claims made about retroviruses, there are several controversial figures who continue to make claims which overall are considered to not have any valid basis or consensus in support of these claims. Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV . Different classes of antiretroviral drugs act on different stages of

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2604-404: The fact that the gene sequences that code for the protease and the reverse transcriptase quickly mutate. These changes in bases cause specific codons and sites with the enzymes to change and thereby avoid drug targeting by losing the sites that the drug actually targets. Because reverse transcription lacks the usual proofreading of DNA replication, a retrovirus mutates very often. This enables

2666-435: The form of independent particles of retroviruses, consist of enveloped particles about 100  nm in diameter. The outer lipid envelope consists of glycoprotein. The virions also contain two identical single-stranded RNA molecules 7–10 kilobases in length. The two molecules are present as a dimer, formed by base pairing between complementary sequences. Interaction sites between the two RNA molecules have been identified as

2728-412: The generation and insertion of new copies of retrotransposons into the host genome. These inserts are transcribed by enzymes of the host into new RNA molecules that enter the cytosol. Next, some of these RNA molecules are translated into viral proteins. The proteins encoded by the gag and pol genes are translated from genome-length mRNAs into Gag and Gag–Pol polyproteins. In example, for the gag gene; it

2790-496: The host genome. Because of this, it can be inserted into oncogenes . In this way some retroviruses can convert normal cells into cancer cells. Some provirus remains latent in the cell for a long period of time before it is activated by the change in cell environment. Studies of retroviruses led to the first demonstrated synthesis of DNA from RNA templates, a fundamental mode for transferring genetic material that occurs in both eukaryotes and prokaryotes . It has been speculated that

2852-430: The initial virion RNA genome. This DNA is often integrated into the host genome, as in the case of retroviruses and pseudoviruses , where it is replicated and transcribed by the host. Group VI includes: The family Retroviridae was previously divided into three subfamilies ( Oncovirinae , Lentivirinae , and Spumavirinae ), but are now divided into two: Orthoretrovirinae and Spumaretrovirinae . The term oncovirus

2914-513: The invading virus particles. The DNA genome is transcribed into both mRNA, for use as a transcript in protein synthesis, and pre-genomic RNA, for use as the template during genome replication. Virally encoded reverse transcriptase uses the pre-genomic RNA as a template for the creation of genomic DNA. Group VII includes: The latter family is closely related to the newly proposed whilst families Belpaoviridae , Metaviridae , Pseudoviridae , Retroviridae , and Caulimoviridae constitute

2976-471: The leukocytes in circulation, but as the blood sample is taken upon the onset of infection, it contains low amount of WBCs, which is why it is termed "pseudoleukopenia". Certain medications can alter the number and function of white blood cells. Medications that can cause leukopenia include clozapine , an antipsychotic medication with a rare adverse effect leading to the total absence of all granulocytes (neutrophils, basophils, eosinophils). Minocycline ,

3038-424: The order Ortervirales . Endogenous retroviruses are not formally included in this classification system, and are broadly classified into three classes, on the basis of relatedness to exogenous genera: Retroviruses have been the focus of several recent claims and assertions which have been largely discredited by the science community. An initial study in 2009 seemed to make new findings which might change some of

3100-537: The plasma membrane after further glycosylation. It is important to note that a retrovirus must "bring" its own reverse transcriptase in its capsid , otherwise it is unable to utilize the enzymes of the infected cell to carry out the task, due to the unusual nature of producing DNA from RNA. Industrial drugs that are designed as protease and reverse-transcriptase inhibitors are made such that they target specific sites and sequences within their respective enzymes. However these drugs can quickly become ineffective due to

3162-673: The prescriber information suggests a complete blood count, including differential cell count, before and after, in particular, high-dose therapy. Immunosuppressive drugs, such as sirolimus , mycophenolate mofetil , tacrolimus , ciclosporin , leflunomide and TNF inhibitors , have leukopenia as a known complication. Interferons used to treat multiple sclerosis , such as interferon beta-1a and interferon beta-1b , can also cause leukopenia. Chemotherapy targets cells that grow rapidly, such as tumors, but can also affect white blood cells, because they are characterized by bone marrow as rapid growing. A common side effect of cancer treatment

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3224-437: The provirus DNA can also cause over expression of regulatory genes. Retroviruses can cause diseases such as cancer and immunodeficiency. If viral DNA is integrated into host chromosomes, it can lead to permanent infections. It is therefore important to discover the body's response to retroviruses. Exogenous retroviruses are especially associated with pathogenic diseases. For example, mice have mouse mammary tumor virus (MMTV), which

3286-785: The retroviral DNA is referred to as a provirus . The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds. Retroviruses have many subfamilies in three basic groups. The specialized DNA-infiltration enzymes in retroviruses make them valuable research tools in molecular biology, and they have been used successfully in gene delivery systems. Evidence from endogenous retroviruses (inherited provirus DNA in animal genomes) suggests that retroviruses have been infecting vertebrates for at least 450 million years. Virions , viruses in

3348-479: The rough endoplasmic reticulum glycosylation begins and the env gene is translated from spliced mRNAs in the rough endoplasmic reticulum, into molecules of the envelope protein. When the envelope protein molecules are carried to the Golgi complex, they are divided into surface glycoprotein and transmembrane glycoprotein by a host protease. These two glycoprotein products stay in close affiliation, and they are transported to

3410-400: The skin, bladder, and respiratory tract, oral disease , seizures , lymphadenopathy (swollen lymph nodes), skin lesions , fatigue , fever , weight loss , stomatitis , gingivitis , litter box avoidance, pancytopenia , recurring bacterial and viral illnesses, anemia , diarrhea and jaundice . Asymptomatic carriers will show no signs of disease, often for many years. The disease has

3472-495: The total genome is about 9,600 base pairs . See the entry on retroviruses for more details on the life cycle of FeLV. In 2006, the United States Department of Agriculture issued a conditional license for a new treatment aid termed Lymphocyte T-Cell Immunomodulator (LTCI). Lymphocyte T-Cell Immunomodulator is manufactured and distributed exclusively by T-Cyte Therapeutics, Inc. Lymphocyte T-Cell Immunomodulator

3534-783: The transferred vector genomes. This technology is of use, not only for research purposes, but also for clinical gene therapy aiming at the long-term correction of genetic defects, e.g., in stem and progenitor cells. Retroviral vector particles with tropism for various target cells have been designed. Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases. Retroviral mutations can be developed to make transgenic mouse models to study various cancers and their metastatic models . Retroviruses that cause tumor growth include Rous sarcoma virus and mouse mammary tumor virus . Cancer can be triggered by proto-oncogenes that were mistakenly incorporated into proviral DNA or by

3596-418: The use of high-dose corticosteroids, broad-spectrum antibiotics to treat opportunistic and comorbid infections, antiviral medications, and immunomodulators such as cyclosporine after requiring multiple packed red blood cell transfusions to raise a critically low blood cell count. Three types of vaccines for FeLV are available: an adjuvanted killed virus noninfectious vaccine, an adjuvanted subunit vaccine, and

3658-405: The usual gene sequence of retroviruses, HTLV-1 contains a fourth region, PX. This region encodes Tax, Rex, p12, p13 and p30 regulatory proteins. The Tax protein initiates the leukemic process and organizes the transcription of all viral genes in the integrated HTLV proviral DNA. Exogenous retroviruses are infectious RNA- or DNA-containing viruses that are transmitted from one organism to another. In

3720-400: The virus has been cleared from the body. Diagnosis can also be made by reference lab testing, using an immunofluorescence (IFA) test. The IFA test uses a blood sample and will detect the virus once it is in the bone marrow by detecting the virus's presence in white blood cells. IFA testing will not give positive results for transient, primary infections - the infection must be persistent to get

3782-481: The virus to grow resistant to antiviral pharmaceuticals quickly, and impedes the development of effective vaccines and inhibitors for the retrovirus. One difficulty faced with some retroviruses, such as the Moloney retrovirus, involves the requirement for cells to be actively dividing for transduction. As a result, cells such as neurons are very resistant to infection and transduction by retroviruses. This gives rise to

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3844-549: Was classically thought to occur only from DNA to RNA, reverse transcriptase transcribes RNA into DNA. The term "retro" in retrovirus refers to this reversal (making DNA from RNA) of the usual direction of transcription. It still obeys the central dogma of molecular biology , which states that information can be transferred from nucleic acid to nucleic acid but cannot be transferred back from protein to either protein or nucleic acid. Reverse transcriptase activity outside of retroviruses has been found in almost all eukaryotes , enabling

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