Trichodysplasia spinulosa is characterized by active polyomavirus infection

Kazem, Siamaque; Meijden, E. van der; Kooijman, Sander; Rosenberg, Arlene S.; Hughey, Lauren C.; Browning, John; Sadler, Genevieve M.; Busam, Klaus J.; Pope, Elena; Benoit, Taylor; Fleckman, Philip; Vries, Esther de; Eekhof, Just; Feltkamp, Mariet C.W.

doi:10.1016/j.jcv.2011.11.007

Cited by 68 publications

(96 citation statements)

References 29 publications

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“…ix new human polyomaviruses have been identified since 2008, including the Merkel cell polyomavirus (MCPyV), associated with Merkel cell carcinoma (1); human polyomaviruses 6, 7, and 9 (HPyV6, HPyV7, and HPyV9) (2-4), not associated with any human disease; trichodysplasia spinulosa polyomavirus (TSPyV), detected in skin lesions of patients with a rare skin disease, trichodysplasia spinulosa (5,6); and the recently discovered Malawi polyomavirus (MWPyV), isolated from stools of a healthy child (7).…”

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confidence: 99%

Age-Specific Seroprevalences of Merkel Cell Polyomavirus, Human Polyomaviruses 6, 7, and 9, and Trichodysplasia Spinulosa-Associated Polyomavirus

Nicol¹,

Robinot²,

Carpentier³

et al. 2013

Clin. Vaccine Immunol.

136

165

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. The presence of specific antibodies against MCPyV, HPyV6, HPyV7, HPyV9, and TSPyV in 828 Italian subjects aged 1 to 100 years was investigated by virus-like particle-based enzyme-linked immunosorbent assays (ELISAs). The findings indicate that all of these new polyomaviruses circulate widely in humans, with seroprevalences in adulthood ranging from 39.4% for HPyV9 to 87.1% for MCPyV, and that primary exposure is most intense in childhood, with the exception of HPyV7 and HPyV9, for which the seroprevalence increased throughout life. The proportion of subjects with high antibody titers was found to increase with age for MCPyV and to decrease with age for TSPyV.

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confidence: 99%

Age-Specific Seroprevalences of Merkel Cell Polyomavirus, Human Polyomaviruses 6, 7, and 9, and Trichodysplasia Spinulosa-Associated Polyomavirus

Nicol¹,

Robinot²,

Carpentier³

et al. 2013

Clin. Vaccine Immunol.

136

165

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“…MCPyV DNA is found in ϳ80% of MCC tumors and is clonally integrated into a subset of these (14). TSPyV has been linked to trichodysplasia spinulosa, a very rare skin condition associated with immunosuppression following organ transplantation (24). It is unclear if the other human polyomaviruses play a role in disease.…”

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confidence: 99%

Identification of MW Polyomavirus, a Novel Polyomavirus in Human Stool

Siebrasse

Reyes

Lim

et al. 2012

J Virol

172

152

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We have discovered a novel polyomavirus present in multiple human stool samples. The virus was initially identified by shotgun pyrosequencing of DNA purified from virus-like particles isolated from a stool sample collected from a healthy child from Malawi. We subsequently sequenced the virus' 4,927-bp genome, which has been provisionally named MW polyomavirus (MWPyV). The virus has genomic features characteristic of the family Polyomaviridae but is highly divergent from other members of this family. It is predicted to encode the large T antigen and small T antigen early proteins and the VP1, VP2, and VP3 structural proteins. A real-time PCR assay was designed and used to screen 514 stool samples from children with diarrhea in St. Louis, MO; 12 specimens were positive for MWPyV. Comparison of the whole-genome sequences of the index Malawi case and one St. Louis case demonstrated that the two strains of MWPyV varied by 5.3% at the nucleotide level. The number of polyomaviruses found in the human body continues to grow, raising the question of how many more species have yet to be identified and what roles they play in humans with and without manifest disease.

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“…Only the results obtained with HeLa are shown. Previously described lesional TS biopsy specimens, stored at Ϫ80°C, were used for RT-PCR and immunohistochemistry (11).…”

Section: Methodsmentioning

confidence: 99%

“…Seven of 13 described human polyomaviruses have been associated with disease in immunocompromised individuals, i.e., JC polyomavirus (JCPyV) (7), BK polyomavirus (BKPyV) (8), Merkel cell polyomavirus (MCPyV) (9), trichodysplasia spinulosa-associated polyomavirus (TSPyV) (10,11), human polyomavirus 6 (HPyV6) (12), human polyomavirus 7 (HPyV7) (13), and New Jersey polyomavirus (NJPyV) (14,15). MCPyV and TSPyV, which belong to orthopolyomavirus lineage I (3,16), are associated with a malignant and a benign hyperproliferative skin disease called Merkel cell carcinoma (MCC) and trichodysplasia spinulosa (TS), respectively.…”

mentioning

confidence: 99%

Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa

Meijden

Kazem

Dargel

et al. 2015

J Virol

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The polyomavirus tumor (T) antigens play crucial roles in viral replication IMPORTANCEThe human trichodysplasia spinulosa-associated polyomavirus (TSPyV) is distinguished among polyomaviruses for combining productive infection with cell-transforming properties. In the research presented here, we further substantiate this unique position by indicating expression of both middle T antigen (MT) and alternative T antigen (ALTO) in TSPyV. So far, none of the human polyomaviruses was shown to express MT, which is considered the most important viral oncoprotein of rodent polyomaviruses. Coexpression of ALTO and MT, which involves a conserved, recently recognized overlapping ORF subject to positive selection, has not been observed before for any polyomavirus. As a result of our findings, this study provides valuable new insights into polyomavirus T gene use and expression. Obviously, these insights will be instrumental in further study and gaining an understanding of TSPyV pathogenicity. More importantly, however, they provide important leads with regard to the interrelationship, functionality, and evolution of polyomaviruses as a whole, indicating that TSPyV is a suitable model virus to study these entities further.H uman polyomaviruses represent a rapidly expanding group of small, circular double-stranded DNA viruses that persistently infect the general population, usually without causing symptoms (1-6). Seven of 13 described human polyomaviruses have been associated with disease in immunocompromised individuals, i.e., JC polyomavirus (JCPyV) (7), BK polyomavirus (BKPyV) (8), Merkel cell polyomavirus (MCPyV) (9), trichodysplasia spinulosa-associated polyomavirus (TSPyV) (10, 11), human polyomavirus 6 (HPyV6) (12), human polyomavirus 7 (HPyV7) (13), and New Jersey polyomavirus (NJPyV) (14, 15). MCPyV and TSPyV, which belong to orthopolyomavirus lineage I (3, 16), are associated with a malignant and a benign hyperproliferative skin disease called Merkel cell carcinoma (MCC) and trichodysplasia spinulosa (TS), respectively. The hyperproliferative phenotype of both diseases indicates involvement of the viral tumor (T) antigens in the patho(onco)genesis.T antigens that play a coordinating role in viral transcription and replication are generally known for their ability to disrupt cellular pathways involved in cell cycle regulation and signaling (17,18). The large T antigen (LT), for example, promotes cell cycle entry through inactivation (hyperphosphorylation) of pRB, as demonstrated, for example, for simian virus 40 (SV40) (18,19).

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Trichodysplasia spinulosa is characterized by active polyomavirus infection

Cited by 68 publications

References 29 publications

Age-Specific Seroprevalences of Merkel Cell Polyomavirus, Human Polyomaviruses 6, 7, and 9, and Trichodysplasia Spinulosa-Associated Polyomavirus

Age-Specific Seroprevalences of Merkel Cell Polyomavirus, Human Polyomaviruses 6, 7, and 9, and Trichodysplasia Spinulosa-Associated Polyomavirus

Identification of MW Polyomavirus, a Novel Polyomavirus in Human Stool

Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa

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