56-397: The primate T-lymphotropic viruses ( PTLVs ) are a group of retroviruses that infect primates, using their lymphocytes to reproduce. The ones that infect humans are known as human T-lymphotropic virus (HTLV), and the ones that infect Old World monkeys are called simian T-lymphotropic viruses (STLVs). PTLVs are named for their ability to cause adult T-cell leukemia/lymphoma , but in
112-440: 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
168-462: 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
224-453: 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
280-446: A host of other proposals. HTLV-3 was discovered in 2005 in rural Cameroon , and were, it is presumed, transmitted from monkeys to hunters of monkeys through bites and scratches. Multiple strains have been identified. A strain has been fully sequenced. PTLV-3 is about 40% different from PTLV-1 and -2. It occasionally cross-reacts with HTLV-2 tests. It is not yet known how much further transmission has occurred among humans, or whether
336-942: 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
392-427: 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
448-470: Is a staple part of their diet. Stump-tail macaques have a large, bulky, muscular build with thick, solid limbs, making them very mobile on land yet quite ungainly in trees, and this unusual physique for a macaque may be responsible for this species unique tendency to consume larger quantities of meat than other macaque species. Stump-tail macaques feed on very large quantities of insects, small animals and eggs. A study population of female stump-tailed macaques
504-450: 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)
560-430: Is common to retroviruses, starting at the envelope glycoprotein (Env) surface subunit (SU) binding to a cellular receptor (in this case GLUT1 and a host of other molecules), and ending with lysis of the cell (in this case, a lymphocyte ). The virion is spherical to pleomorphic, about 80-100 nm in diameter. Unusually, the single-stranded RNA genome is present in two copies, forming a dimer speficially packed by parts of
616-506: 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,
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#1732765328588672-475: Is not found in dry forests except where it ranges in the Himalayan region of India, only spending time in secondary forests if it is bordering old-growth forest tropical forests. With its thick fur, the stump-tailed macaque can live in cold climates at elevations up to 4,000 m (13,000 ft). It is distributed from northeastern India and southern China into the northwest tip of West Malaysia on
728-514: 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
784-579: Is the medically most important species in the class. Discovered by Robert Gallo and colleagues in 1980, HTLV-1 has been implicated in several kinds of diseases, including tropical spastic paraparesis and as a virus cancer link for adult T-cell leukemia/lymphoma . Between 1 in 20 and 1 in 25 infected people are thought to develop cancer as a result of the virus. STLV-1 is oncogenic in Japanese macaques. HTLV-1 has seven reported subtypes (subtypes A through G). The great majority of infections are caused by
840-408: Is the more clinically significant of the two: at least 500,000 of the individuals infected with HTLV-1 eventually develop an often rapidly fatal leukemia , while others will develop a debilitative myelopathy , and yet others will experience uveitis , infectious dermatitis , or another inflammatory disorder. HTLV-2 is associated with milder neurologic disorders and chronic pulmonary infections . In
896-401: Is the prototypical PTLV, from which comparisons are drawn for the newly-known types. A retrovirus , PTLV shares the common gag-pro-pol-env set of genes, yet shows great complexity in the unique 3' end. These new proteins provide a great source of new adaptive function: HTLV-1 has three tandem imperfect 21-base repeats as the long terminal repeat , but other PTLVs only have two. The lifecycle
952-578: Is their ability to defuse intense confrontations and maintain a high degree of pacifism and harmony in their troop, thanks to their surprisingly rich repertoire of reconciliation tactics. This species has no lasting pair bonds and is truly promiscuous, a staple for macaques. Physical violence very rarely occurs, and although minor scraps often flair up and physical intimidation displays occur, they tend to quickly be resolved, resulting in this species being labelled as peaceful. Stump-tailed macaques are remarkably unfussy in their eating habits though fruit generally
1008-543: 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
1064-512: 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
1120-707: The Malay Peninsula . It is also found in Burma , Thailand , Laos , Cambodia and Vietnam . It is possibly extinct in Bangladesh . No global population estimate is available. In Cambodia, a declining population of 230 is reported from Keo Seima Wildlife Sanctuary . A study population was introduced to Tanaxpillo , an uninhabited island in Lake Catemaco , Veracruz , Mexico in 1974, where it ranges in seminatural conditions. Most information on
1176-1310: The bear macaque , is a species of macaque native to South Asia and Southeast Asia . In India, it occurs south of the Brahmaputra River , in the northeastern part of the country. Its range in India extends from Assam and Meghalaya to eastern Arunachal Pradesh, Nagaland, Manipur, Mizoram and Tripura. It is primarily frugivorous , but eats many types of vegetation, such as seeds, leaves and roots, but also hunts freshwater crabs , frogs , bird eggs and insects . The stump-tailed macaque has long, thick, dark brown fur covering its body, but its face and its short tail, which measures between 32 and 69 mm (1.3 and 2.7 in), are hairless. Infants are born white and darken as they mature. As they age, their bright pink or red faces darken to brown or nearly black and lose most of their hair. Males are larger than females, measuring 51.7–65 cm (20.4–25.6 in) long and weighing 9.7–10.2 kg (21–22 lb), while females measure 48.5–58.5 cm (19.1–23.0 in) and weigh 7.5–9.1 kg (17–20 lb). Males' canine teeth , which are important for establishing dominance within social groups, are more elongated than those of
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#17327653285881232-419: The gag protein. The use of "HTLV-3" can cause some confusion, because the name HTLV-III was one of the names for HIV in early AIDS literature, but has since fallen out of use. The name HTLV-IV has also been used to describe HIV-2 . A large Canadian study documented this confusion among healthcare workers, where >90% of HTLV tests ordered by physicians were actually intended to be HIV tests. PTLV-1
1288-427: 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
1344-591: 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). Macaca arctoides The stump-tailed macaque ( Macaca arctoides ), also called
1400-467: The ICTV (P/H/STLV-1, -2, -3), plus two that are reported but unrecognized (HTLV-4, STLV-5). The first known, and still most medically important PTLV is HTLV-1, discovered in 1980. HTLVs belong to the genus Deltaretrovirus . The only other recognized species in the genus is Bovine leukemia virus , an economically-important cattle pathogen. As its name suggests, this virus causes leukemia in cows. HTLV-1
1456-486: 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
1512-682: 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
1568-684: The United States, HTLV-1/2 seroprevalence rates among volunteer blood donors average 0.016 percent. No specific illnesses have yet been associated with HTLV-3 and HTLV-4 . While there is no present licensed vaccine, there are many factors which make a vaccine against HTLV-1 feasible. The virus displays relatively low antigenic variability, natural immunity does occur in humans, and experimental vaccination using envelope antigens has been shown to be successful in animal models. Plasmid DNA vaccines elicit potent and protective immune responses in numerous small-animal models of infectious diseases. However, their immunogenicity in primates appears less potent. In
1624-457: The case of HTLV-1 it can also cause a demyelinating disease called tropical spastic paraparesis . On the other hand, newer PTLVs are simply placed into the group by similarity and their connection to human disease remains unclear. HTLVs have evolved from STLVs by interspecies transmission . Within each species of PTLV, the HTLV is more similar to its cognate STLV than to the other HTLVs. There are currently three species of PTLVs recognized by
1680-403: The cosmopolitan subtype A. The HTLV-I/STLV-I history might suggest a simian migration from Asia to Africa not much earlier than 19,500–60,000 years ago. Discovered in 1982, HTLV-2 has not yet been conclusively linked to any disease. It generally causes no symptoms. It might impact the platelet count, contribute to chronic lung infections, or lead to future cutaneous T-cell lymphoma (CTCL), among
1736-399: 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
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1792-480: The cure of a patient in Greece; tenofovir disoproxil (TDF), a reverse-transcriptase inhibitor used for HIV; cepharanthine , an alkaloid from stephania cepharantha hayata; and phosphonated carbocyclic 2'-oxa-3'aza nucleosides (PCOANs). A newer formulation of TDF, called tenofovir alafenamide (TAF), also has promise as a treatment with less toxicity. Retrovirus A retrovirus is a type of virus that inserts
1848-409: 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
1904-419: 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
1960-471: 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
2016-404: 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
2072-433: The females. Like all macaques, this species has cheek pouches to store food for short periods of time. This Old World monkey travels quadrupedally , usually on the ground, as it is not very agile in trees. It is generally found in evergreen tropical and subtropical moist broadleaf forests , at different elevations depending on the amount of rainfall in the area. It depends on rainforests for food and shelter, and
2128-435: 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
2184-412: 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
2240-496: 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
2296-624: The induction of neutralizing antibodies, as well as a strategy to generate a multivalent cytotoxic T-lymphocyte (CTL) response against the HTLV-1 Tax antigen. A vaccine candidate that can elicit or boost anti-gp46 neutralizing antibody response may have a potential for prevention and therapy against HTLV-1 infection. Potential treatments include prosultiamine , a vitamin B-1 derivative, which has been shown to reduce viral load and symptoms; azacytidine , an anti-metabolite, which has been credited with
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2352-430: 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
2408-513: 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
2464-424: 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
2520-400: The past two decades a large initiative has been put forth to understand the biological and pathogenic properties of the human T-cell lymphotropic virus type 1 (HTLV-1); this has ultimately led to the development of various experimental vaccination and therapeutic strategies to combat HTLV-1 infection. These strategies include the development of envelope glycoprotein derived B-cell epitopes for
2576-537: 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
2632-437: 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
2688-785: 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
2744-483: 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
2800-470: The species comes from the introduced population on Tanaxpillo and other captive settings, as few long-term studies have been conducted on the stump-tailed macaque in the wild. Stump-tailed macaque generally share the same social structure of any macaque species with a linear dominance hierarchy that is rigid and hereditary in females yet fluctuates among males based on their fighting ability and social maneuvering, but what makes stump-tail macaques truly unique
2856-783: 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
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#17327653285882912-405: 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
2968-681: The virus can cause disease. HTLV-4 was discovered at the same site as HTLV-3 in 2005. Even less is known about this virus, as no simian counterpart has ever been found As of 2011. ICTV does not recognize it as a species. The sequence is, however, available. STLV-5 is a name used for a highly divergent PTLV-1 strain isolated from Macaca arctoides . HTLV-1 and HTLV-2 can be transmitted sexually , by blood to blood contact (e.g. by blood transfusion or sharing needles when using drugs) and via breast feeding . Two HTLVs are well established. HTLV-1 and HTLV-2 are both involved in actively spreading epidemics, affecting 15–20 million people worldwide. HTLV-1
3024-486: 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
3080-549: 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
3136-400: Was found to have increased levels of steroid sex hormones, specifically 17β-estradiol and progesterone levels. 17β-estradiol levels were significantly greater during summer and fall and progesterone levels were significantly greater during summer, fall and winter. This explains how stump-tailed macaques have two mating seasons per year: one in summer (July–August) and one in fall (November). This
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