Trichodysplasia spinulosa polyomavirus

Trichodysplasia spinulosa polyomavirus (also known as Trichodysplasia spinulosa-associated polyomavirus, abbreviated TSPyV or TSV) is a member virus of Human polyomavirus 8[1] that infects human hosts. First discovered in 2010, TSPyV is associated with Trichodysplasia spinulosa, a rare skin disease only seen in immunocompromised patients.[2] The virus causes hyperproliferation and enlargement of hair follicles by modulating PP2A protein phosphatase signaling pathways.[3] TSPyV was the eighth human polyomavirus to be discovered, and one of four associated with human disease, out of 13 human polyomaviruses known as of the 2015 update to polyomavirus taxonomy released by the International Committee on Taxonomy of Viruses.[4][5][6]

Trichodysplasia spinulosa-associated polyomavirus
Virus classification
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cossaviricota
Class: Papovaviricetes
Order: Sepolyvirales
Family: Polyomaviridae
Genus: Alphapolyomavirus
Species: Human polyomavirus 8
Virus:
Trichodysplasia spinulosa-associated polyomavirus
Synonyms
  • Trichodysplasia spinulosa polyomavirus

Structure and genome
A map of the genome of TSPyV as described at its discovery in 2010.[2] Subsequent work has indicated the possible presence of additional genes.[7]

Like all polyomaviruses, TSPyV has a circular double-stranded DNA genome of around 5.2 kilobases. The genome was originally reported to contain five genes in an organization typical of polyomaviruses, with the small tumor antigen and large tumor antigen genes located in the "early" region of the genome expressed early in the infection cycle, and the viral capsid genes VP1, VP2, and VP3 expressed from the late region.[2] A subsequent study of gene expression during TSPyV infection identified messenger RNA consistent with middle tumor antigen, an early-region protein whose homologs had previously only been reported in polyomaviruses that infect rodents. Middle tumor antigen in mouse and hamster polyomavirus has been closely associated with these viruses' ability to cause tumors. The same study also observed evidence of an additional protein, called tiny T, and of an alternatively spliced form of large tumor antigen known as ALTO.[7]

Clinical manifestations

Trichodysplasia spinulosa is a proliferative skin disorder[8][9] that occurs in immunocompromised people and is considered benign, but can be disfiguring.[10] It was suspected to be associated with viral infection on the basis of the patient population in which it appeared, and electron microscopy studies of clinical samples identified virus-like particles of a size and shape consistent with a polyomavirus.[11][12] Unlike Merkel cell carcinoma caused mostly by Merkel cell polyomavirus, trichodysplasia spinulosa is a dysplasia rather than a neoplasia.[13] TSPyV appears to actively replicate in the hair follicle inner root sheath cells; hyperproliferation of these cells is thought to underlie the clinically observable manifestations of the disease.[9][13] Antiviral drugs such as valganciclovir and cidofovir have shown benefit in treating this disorder in case reports.[14][15]

Epidemiology

As with most human polyomaviruses, TSPyV is a common asymptomatic infection in healthy adults. Estimates of seroprevalence - that is, prevalence of detectable antibodies against viral proteins - in immunocompetent adults range from 70 to 80% in different sample populations.[9][16][17] TSPyV infects the skin, but viral DNA is rarely detectable there in asymptomatic individuals even if they possess antibodies to the virus indicating exposure.[9] TSPyV has been associated with disease only in severely immunocompromised individuals, and then only in a small minority of those in whom the virus is detectable. Individuals with TS symptoms exhibit much higher viral loads than do asymptomatically infected immunocompromised individuals.[2][9]

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References
  1. "Genus: Alphapolyomavirus" (html). International Committee on Taxonomy of Viruses (ICTV). Retrieved 17 June 2019.
  2. Van der Meijden, E; Janssens, RWA; Lauber, C; Bouwes Bavinck, JN; Gorbalenya, AE; et al. (2010). "Discovery of a New Human Polyomavirus Associated with Trichodysplasia Spinulosa in an Immunocompromized Patient". PLoS Pathog. 6 (7): e1001024. doi:10.1371/journal.ppat.1001024. PMC 2912394. PMID 20686659.
  3. Nguyen, HP; Patel, A; Simonette, RA; Rady, PL; Tyring, SK; et al. (2014). "Binding of the Trichodysplasia Spinulosa–Associated Polyomavirus Small T Antigen to Protein Phosphatase 2A: Elucidation of a Potential Pathogenic Mechanism in a Rare Skin Disease". JAMA Dermatology. 150 (11): 1234–1236. doi:10.1001/jamadermatol.2014.1095. PMID 25389794.
  4. ICTV. "Virus Taxonomy: 2015 Release". Retrieved 26 July 2016.
  5. Polyomaviridae Study Group of the International Committee on Taxonomy of, Viruses; Calvignac-Spencer, S; Feltkamp, MC; Daugherty, MD; Moens, U; Ramqvist, T; Johne, R; Ehlers, B (29 February 2016). "A taxonomy update for the family Polyomaviridae". Archives of Virology. 161 (6): 1739–50. doi:10.1007/s00705-016-2794-y. hdl:10037/13151. PMID 26923930.
  6. DeCaprio, JA; Garcea, RL (2013). "A cornucopia of human polyomaviruses". Nat. Rev. Microbiol. 11 (4): 264–76. doi:10.1038/nrmicro2992. PMC 3928796. PMID 23474680.
  7. van der Meijden, Els; Kazem, Siamaque; Dargel, Christina A.; van Vuren, Nick; Hensbergen, Paul J.; Feltkamp, Mariet C. W.; Imperiale, M. J. (15 September 2015). "Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa". Journal of Virology. 89 (18): 9427–9439. doi:10.1128/JVI.00911-15. PMC 4542345. PMID 26136575.
  8. Kazem, Siamaque; van der Meijden, Els; Wang, Richard C.; Rosenberg, Arlene S.; Pope, Elena; Benoit, Taylor; Fleckman, Philip; Feltkamp, Mariet C. W.; Deb, Sumitra (7 October 2014). "Polyomavirus-Associated Trichodysplasia Spinulosa Involves Hyperproliferation, pRB Phosphorylation and Upregulation of p16 and p21". PLoS ONE. 9 (10): e108947. Bibcode:2014PLoSO...9j8947K. doi:10.1371/journal.pone.0108947. PMC 4188587. PMID 25291363.
  9. Kazem, Siamaque; van der Meijden, Els; Feltkamp, Mariet C. W. (August 2013). "The trichodysplasia spinulosa-associated polyomavirus: virological background and clinical implications". APMIS. 121 (8): 770–782. doi:10.1111/apm.12092. PMID 23593936.
  10. Wu, J.H.; Nguyen, H.P.; Rady, P.L.; Tyring, S.K. (March 2016). "Molecular insight into the viral biology and clinical features of trichodysplasia spinulosa". British Journal of Dermatology. 174 (3): 490–498. doi:10.1111/bjd.14239. PMID 26479880.
  11. Haycox, CL; Kim, S; Fleckman, P; Smith, LT; Piepkorn, M; Sundberg, JP; Howell, DN; Miller, SE (December 1999). "Trichodysplasia spinulosa--a newly described folliculocentric viral infection in an immunocompromised host". The Journal of Investigative Dermatology. Symposium Proceedings. 4 (3): 268–71. doi:10.1038/sj.jidsp.5640227. PMID 10674379.
  12. Osswald, Sandra S.; Kulick, Kevin B.; Tomaszewski, Maria-Magdalena; Sperling, Leonard C. (September 2007). "Viral-associated trichodysplasia in a patient with lymphoma: a case report and review". Journal of Cutaneous Pathology. 34 (9): 721–725. doi:10.1111/j.1600-0560.2006.00693.x. PMID 17696921.
  13. Kazem, Siamaque; van der Meijden, Els; Kooijman, Sander; Rosenberg, Arlene S.; Hughey, Lauren C.; Browning, John C.; Sadler, Genevieve; Busam, Klaus; Pope, Elena; Benoit, Taylor; Fleckman, Philip; de Vries, Esther; Eekhof, Just A.; Feltkamp, Mariet C.W. (March 2012). "Trichodysplasia spinulosa is characterized by active polyomavirus infection". Journal of Clinical Virology. 53 (3): 225–230. doi:10.1016/j.jcv.2011.11.007. PMID 22196870.
  14. Holzer, Aton M.; Hughey, Lauren C. (January 2009). "Trichodysplasia of immunosuppression treated with oral valganciclovir". Journal of the American Academy of Dermatology. 60 (1): 169–172. doi:10.1016/j.jaad.2008.07.051. PMC 2708076. PMID 19103376.
  15. Wanat, Karolyn A. (1 February 2012). "Viral-Associated Trichodysplasia". Archives of Dermatology. 148 (2): 219–223. doi:10.1001/archdermatol.2011.1413. PMC 3346264. PMID 22351821.
  16. van der Meijden, E; Kazem, S; Burgers, MM; Janssens, R; Bouwes Bavinck, JN; de Melker, H; Feltkamp, MC (August 2011). "Seroprevalence of trichodysplasia spinulosa-associated polyomavirus". Emerging Infectious Diseases. 17 (8): 1355–63. doi:10.3201/eid1708.110114. PMC 3381547. PMID 21801610.
  17. Gossai, A; Waterboer, T; Nelson, HH; Michel, A; Willhauck-Fleckenstein, M; Farzan, SF; Hoen, AG; Christensen, BC; Kelsey, KT; Marsit, CJ; Pawlita, M; Karagas, MR (1 January 2016). "Seroepidemiology of Human Polyomaviruses in a US Population". American Journal of Epidemiology. 183 (1): 61–9. doi:10.1093/aje/kwv155. PMC 5006224. PMID 26667254.

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