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Primate T-lymphotropic virus

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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 the case of HTLV-1 it can also cause a demyelinating disease called tropical spastic paraparesis.[2] On the other hand, newer PTLVs are simply placed into the group by similarity and their connection to human disease remains unclear.[1]

Primate T-lymphotropic virus
a micrograph showing both Human T-lymphotropic virus 1 and HIV
a micrograph showing both Human T-lymphotropic virus 1 and HIV
Scientific classificationEdit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Deltaretrovirus
Groups included

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.[1] There are currently three species of PTLVs recognized by the ICTV (P/H/STLV-1, -2, -3), plus two that are reported but unrecognized (HTLV-4, STLV-5).[1] The first known, and still most medically important PTLV is HTLV-1, discovered in 1980.[3]

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.[4]

General virology

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Genomic organization of Deltaretrovirues; gag-pro-pol part trimmed off.

HTLV-1 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:[5]

  • Tax, the transactivator, is common to all Deltaretrovirus. In a HTLV-1 infection, it is the first protein to be expressed, and in turn is responsible for the expression of the provirus at the LTR during the early phase.[6]
  • Rex is also common to all extant Deltaretrovirus. As it gets expressed, Rex binds mRNA to control the extent of splicing.[6]
  • HBZ is the first novel protein, only common among PLTV. It encodes a basic leucine zipper, and is known to be enhance HLTV-1 replication and oncogenicity. It is encoded in the opposite ("antisense") direction compared to all other ORFs.[6]
  • p12, p8, p30, p13 are the newest class of proteins only found in HTLV-1.[7]

HTLV-1 has three tandem imperfect 21-base repeats as the long terminal repeat, but other PTLVs only have two.[1]

The lifecycle 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),[8] and ending with lysis of the cell (in this case, a lymphocyte).[9] 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 specifically packed by parts of the gag protein.[10]

Nomenclatural clarification

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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.[11] The name HTLV-IV has also been used to describe HIV-2.[12] 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.[13]

PTLV-1

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Main article: HTLV-1

PTLV-1 is the medically most important species in the class. Discovered by Robert Gallo and colleagues in 1980,[14] 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.[citation needed][15] STLV-1 is oncogenic in Japanese macaques.[16]

HTLV-1 has seven reported subtypes (subtypes A through G).[17] The great majority of infections are caused by the cosmopolitan subtype A.[18] 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.[19]

HTLV-2

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Main article: Human T-lymphotropic virus 2

Discovered in 1982,[20] HTLV-2 has not yet been conclusively linked to any disease.[21] It generally causes no symptoms. It might impact the platelet count,[22] contribute to chronic lung infections,[23] or lead to future cutaneous T-cell lymphoma (CTCL),[24] among a host of other proposals.

HTLV-3

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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.[25][26] Multiple strains have been identified.[27] A strain has been fully sequenced.[28][29]

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 the virus can cause disease.[1]

HTLV-4

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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.[1]

STLV-5

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STLV-5 is a name used for a highly divergent PTLV-1 strain isolated from Macaca arctoides.[1]

Transmission

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HTLV-1 and HTLV-2 can be transmitted sexually,[30][31] by blood to blood contact (e.g. by blood transfusion or sharing needles when using drugs)[32][33] and via breast feeding.[34]

Epidemiology

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Two HTLVs are well established. HTLV-1 and HTLV-2 are both involved in actively spreading epidemics, affecting 15–20 million people worldwide.[35]

HTLV-1 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 the United States, HTLV-1/2 seroprevalence rates among volunteer blood donors average 0.016 percent.[citation needed]

No specific illnesses have yet been associated with HTLV-3 and HTLV-4.

Vaccination and treatments

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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 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 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.[36]

Potential treatments include prosultiamine, a vitamin B-1 derivative, which has been shown to reduce viral load and symptoms;[37] azacytidine, an anti-metabolite, which has been credited with the cure of a patient in Greece;[38] tenofovir disoproxil (TDF), a reverse-transcriptase inhibitor used for HIV; cepharanthine, an alkaloid from Stephania cephalantha Hayata;[39] and phosphonated carbocyclic 2'-oxa-3'aza nucleosides (PCOANs).[40] A newer formulation of TDF, called tenofovir alafenamide (TAF), also has promise as a treatment with less toxicity.[citation needed]

References

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  1. ^ a b c d e f g h i Mahieux, R; Gessain, A (July 2011). "HTLV-3/STLV-3 and HTLV-4 viruses: discovery, epidemiology, serology and molecular aspects". Viruses. 3 (7): 1074–90. doi:10.3390/v3071074. PMC 3185789. PMID 21994771.
  2. ^ "Recommendations for counseling persons infected with human T-lymphotrophic virus, types I and II. Centers for Disease Control and Prevention and U.S. Public Health Service Working Group". MMWR Recomm Rep. 42 (RR-9): 1–13. 1993. PMID 8393133. Archived from the original on 2017-08-29. Retrieved 2017-09-09.
  3. ^ Verdonck, Kristien; González, Elsa; Van Dooren, Sonia; Vandamme, Anne-Mieke; Vanham, Guido; Gotuzzo, Eduardo (April 2007). "Human T-lymphotropic virus 1: recent knowledge about an ancient infection". The Lancet Infectious Diseases. 7 (4): 266–281. doi:10.1016/S1473-3099(07)70081-6. PMID 17376384.
  4. ^ Hron, T; Elleder, D; Gifford, RJ (27 November 2019). "Deltaretroviruses have circulated since at least the Paleogene and infected a broad range of mammalian species". Retrovirology. 16 (1): 33. doi:10.1186/s12977-019-0495-9. PMC 6882180. PMID 31775783.
  5. ^ Pavesi, Angelo; Magiorkinis, Gkikas; Karlin, David G. (15 August 2013). "Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the "Gene Nursery" of Deltaretroviruses". PLOS Computational Biology. 9 (8): e1003162. Bibcode:2013PLSCB...9E3162P. doi:10.1371/journal.pcbi.1003162. PMC 3744397. PMID 23966842.
  6. ^ a b c Nakano, K; Watanabe, T (2012). "HTLV-1 Rex: the courier of viral messages making use of the host vehicle". Frontiers in Microbiology. 3: 330. doi:10.3389/fmicb.2012.00330. PMC 3434621. PMID 22973269.
  7. ^ Bai, XT; Nicot, C (2012). "Overview on HTLV-1 p12, p8, p30, p13: accomplices in persistent infection and viral pathogenesis". Frontiers in Microbiology. 3: 400. doi:10.3389/fmicb.2012.00400. PMC 3518833. PMID 23248621.
  8. ^ Ghez, D; Lepelletier, Y; Jones, KS; Pique, C; Hermine, O (29 November 2010). "Current concepts regarding the HTLV-1 receptor complex". Retrovirology. 7: 99. doi:10.1186/1742-4690-7-99. PMC 3001707. PMID 21114861.
  9. ^ "Primate T-lymphotropic virus 1 ~ ViralZone". viralzone.expasy.org.
  10. ^ Wu, W; Hatterschide, J; Syu, YC; Cantara, WA; Blower, RJ; Hanson, HM; Mansky, LM; Musier-Forsyth, K (19 October 2018). "Human T-cell leukemia virus type 1 Gag domains have distinct RNA-binding specificities with implications for RNA packaging and dimerization". The Journal of Biological Chemistry. 293 (42): 16261–16276. doi:10.1074/jbc.RA118.005531. PMC 6200928. PMID 30217825.
  11. ^ Human+T-Lymphotropic+Virus+Type+III at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  12. ^ Human+T+Lymphotropic+Virus+Type+IV at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  13. ^ Siemieniuk, Reed; Fonseca, Kevin; Gill M. John (November 2012). "Using Root Cause Analysis and Form Redesign to Reduce Incorrect Ordering of HIV Tests". The Joint Commission Journal on Quality and Patient Safety. 11. 38 (11): 506–512. doi:10.1016/S1553-7250(12)38067-7. PMID 23173397.
  14. ^ Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (1980). "Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma". Proc. Natl. Acad. Sci. U.S.A. 77 (12): 7415–9. Bibcode:1980PNAS...77.7415P. doi:10.1073/pnas.77.12.7415. PMC 350514. PMID 6261256.
  15. ^ WELSH, JAMES S. (January 2011). "Contagious Cancer". The Oncologist. 16 (1): 1–4. doi:10.1634/theoncologist.2010-0301. PMC 3228048. PMID 21212437.
  16. ^ Miura, Michi; Tanabe, Junko; Sugata, Kenji; Zhao, Tiejun; Ma, Guangyong; Miyazato, Paola; Yasunaga, Jun-Ichiro; Matsuoka, Masao (2014). "STLV-1-infected Japanese macaque as a model of HTLV-1 infection". Retrovirology. 11 (Suppl 1): O12. doi:10.1186/1742-4690-11-S1-O12. PMC 4042625.
  17. ^ Verdonck, Kristien; González, Elsa; Van Dooren, Sonia; Vandamme, Anne-Mieke; Vanham, Guido; Gotuzzo, Eduardo (April 2007). "Human T-lymphotropic virus 1: recent knowledge about an ancient infection". The Lancet Infectious Diseases. 7 (4): 266–281. doi:10.1016/S1473-3099(07)70081-6. PMID 17376384.
  18. ^ Gonçalves DU, Proietti FA, Ribas JG, Araújo MG, Pinheiro SR, Guedes AC, Carneiro-Proietti AB (2010). "Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases". Clin. Microbiol. Rev. 23 (3): 577–89. doi:10.1128/CMR.00063-09. PMC 2901658. PMID 20610824.
  19. ^ Salemi M, Desmyter J, Vandamme AM (March 2000). "Tempo and mode of human and simian T-lymphotropic virus (HTLV/STLV) evolution revealed by analyses of full-genome sequences". Molecular Biology and Evolution. 17 (3): 374–86. doi:10.1093/oxfordjournals.molbev.a026317. PMID 10723738.
  20. ^ Kalyanaraman VS, Sarngadharan MG, Robert-Guroff M, Miyoshi I, Golde D, Gallo RC (November 1982). "A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia". Science. 218 (4572): 571–3. Bibcode:1982Sci...218..571K. doi:10.1126/science.6981847. PMID 6981847.
  21. ^ "HTLV Type I and Type II". NORD (National Organization for Rare Disorders). Retrieved 2019-02-22.
  22. ^ Bartman MT, Kaidarova Z, Hirschkorn D, et al. (November 2008). "Long-term increases in lymphocytes and platelets in human T-lymphotropic virus type II infection". Blood. 112 (10): 3995–4002. doi:10.1182/blood-2008-05-155960. PMC 2581993. PMID 18755983.
  23. ^ "Human T-cell leukemia virus type 2". US Department of Health and Human Services | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Retrieved 2019-02-22.   This article incorporates text from this source, which is in the public domain.
  24. ^ Mirvish, Ezra D.; Pomerantz, Rebecca G.; Geskin, Larisa J. (2011). "Infectious agents in cutaneous T-cell lymphoma". Journal of the American Academy of Dermatology. 64 (2): 423–431. doi:10.1016/j.jaad.2009.11.692. PMC 3954537. PMID 20692726.
  25. ^ Mahieux, R.; Gessain, Antoine (2009). "The human HTLV-3 and HTLV-4 retroviruses: New members of the HTLV family". Pathologie Biologie. 57 (2): 161–6. doi:10.1016/j.patbio.2008.02.015. PMID 18456423.
  26. ^ Mahieux, R; Gessain, A (2005). "Les nouveaux rétrovirus humains HTLV-3 et HTLV-4" [New human retroviruses: HTLV-3 and HTLV-4] (PDF). Médecine Tropicale (in French). 65 (6): 525–8. PMID 16555510. Archived (PDF) from the original on 2011-07-15. Retrieved 2010-12-10.
  27. ^ Calattini, Sara; Betsem, Edouard; Bassot, Sylviane; Chevalier, SéBastien Alain; Mahieux, Renaud; Froment, Alain; Gessain, Antoine (2009). "New Strain of Human T Lymphotropic Virus (HTLV) Type 3 in a Pygmy from Cameroon with Peculiar HTLV Serologic Results" (PDF). The Journal of Infectious Diseases. 199 (4): 561–4. doi:10.1086/596206. PMID 19099485. Archived (PDF) from the original on 2019-09-01. Retrieved 2019-09-01.
  28. ^ Calattini, S.; Chevalier, S. A.; Duprez, R.; Afonso, P.; Froment, A.; Gessain, A.; Mahieux, R. (2006). "Human T-Cell Lymphotropic Virus Type 3: Complete Nucleotide Sequence and Characterization of the Human Tax3 Protein". Journal of Virology. 80 (19): 9876–88. doi:10.1128/JVI.00799-06. PMC 1617244. PMID 16973592.
  29. ^ Chevalier, S. A.; Ko, N. L.; Calattini, S.; Mallet, A.; Prevost, M.-C.; Kehn, K.; Brady, J. N.; Kashanchi, F.; et al. (2008). "Construction and Characterization of a Human T-Cell Lymphotropic Virus Type 3 Infectious Molecular Clone". Journal of Virology. 82 (13): 6747–52. doi:10.1128/JVI.00247-08. PMC 2447071. PMID 18417569.
  30. ^ Rodriguez, Evelyn M.; de Moya, E. Antonio; Guerrero, Ernesto; Monterroso, Edgar R.; Quinn, Thomas C.; Puello, Elizardo; de Quiñones, Margarita Rosado; Thorington, Bruce; et al. (1993). "HIV-1 and HTLV-I in sexually transmitted disease clinics in the Dominican Republic". Journal of Acquired Immune Deficiency Syndromes. 6 (3): 313–8. PMID 8450407. Archived from the original on 2012-10-06. Retrieved 2010-12-10.
  31. ^ Roucoux, Diana F.; Wang, Baoguang; Smith, Donna; Nass, Catharie C.; Smith, James; Hutching, Sheila T.; Newman, Bruce; Lee, Tzong-Hae; et al. (2005). "A Prospective Study of Sexual Transmission of Human T Lymphotropic Virus (HTLV)-I and HTLV-II". The Journal of Infectious Diseases. 191 (9): 1490–7. doi:10.1086/429410. PMID 15809908.
  32. ^ "Die Vorteile eines GPS-Tracking-Halsbandes für Hunde - HTLV1 Hunde GPS Tracker Vergleich". Archived from the original on 2015-11-02. Retrieved 2015-11-04.
  33. ^ "Grundlagen der Druckluft Drehdurchführungen – htlv1.eu". Archived from the original on 2015-11-20. Retrieved 2015-11-04.
  34. ^ Coovadia HM, Rollins NC, Bland RM, Little K, Coutsoudis A, Bennish ML, Newell ML (2007). "Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study". Lancet. 369 (9567): 1107–16. doi:10.1016/S0140-6736(07)60283-9. PMID 17398310. S2CID 6183061.
  35. ^ de Thé, G.; Kazanji, M. (1996). "An HTLV-I/II vaccine: from animal models to clinical trials?". Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology. 13 (Suppl 1): S191–198. doi:10.1097/00042560-199600001-00029. ISSN 1077-9450. PMID 8797723.
  36. ^ Tanaka Y, Takahashi Y, Kodama A, Tanaka R, Saito M (2014). "Neutralizing antibodies against human T cell leukemia virus type-I (HTLV-1) eradicate HTLV-1 in combination with autologous peripheral blood mononuclear cells via antibody-dependent cellular cytotoxicity while preventing new infection" (PDF). Retrovirology. 11 (Suppl 1): O39. doi:10.1186/1742-4690-11-s1-o39. PMC 4044937. S2CID 7065527. Archived (PDF) from the original on 2015-09-10. Retrieved 2014-03-05.
  37. ^ "Nervous System Disease: A New Outlet for an Old Drug?". Archived from the original on 2018-01-18. Retrieved 2018-03-09.
  38. ^ Diamantopoulos PT, Michael M, Benopoulou O, Bazanis E, Tzeletas G, Meletis J, Vayopoulos G, Viniou NA (2012). "Antiretroviral activity of 5-azacytidine during treatment of a HTLV-1 positive myelodysplastic syndrome with autoimmune manifestations". Virol. J. 9: 1. doi:10.1186/1743-422X-9-1. PMC 3305386. PMID 22214262.
  39. ^ Toyama, M; Hamasaki, T; Uto, T; Aoyama, H; Okamoto, M; Hashmoto, Y; Baba, M (2012). "Synergistic inhibition of HTLV-1-infected cell proliferation by combination of cepharanthine and a tetramethylnaphthalene derivative". Anticancer Research. 32 (7): 2639–45. PMID 22753721.
  40. ^ MacChi, B.; Balestrieri, E.; Ascolani, A.; Hilburn, S.; Martin, F.; Mastino, A.; Taylor, G. P. (2011). "Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors". Viruses. 3 (12): 469–483. doi:10.3390/v3050469. PMC 3185762. PMID 21994743.
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