Polyomaviruses of the Skin: Integrating Molecular and Clinical Advances in an Emerging Class of Viruses

J.C. Sheu; J. Tran; P.L. Rady; H. Dao Jr; S.K. Tyring; H.P. Nguyen

Disclosures

The British Journal of Dermatology. 2019;180(6):1302-1311. 

In This Article

Abstract and Introduction

Abstract

Background: Human polyomaviruses (HPyVs) are small, nonenveloped, double-stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus – Merkel cell polyomavirus (MCPyV) – six more species have been detected in the skin: trichodysplasia spinulosa-associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology.

Results: In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs.

Conclusions:We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV-associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.

Introduction

Human polyomaviruses (HPyVs) are small, nonenveloped viruses with circular, double-stranded DNA.[1–3] The first HPyVs were described in 1971 when the BK virus and JC virus were predominantly linked to nephropathy and progressive multifocal leucoencephalopathy, respectively, in immunosuppressed patients.[4,5] In 2007, two more HPyVs were discovered, KI virus and WU virus, but their associations with human disease, if any, have yet to be identified.[6–8] It was not until 2008, with the discovery of the Merkel cell polyomavirus (MCPyV) as an aetiology of the cutaneous tumour Merkel cell carcinoma (MCC), that a species of HPyV was causally linked to either human carcinogenesis or skin disease.[9,10] Since then, nine other HPyV species have been discovered, of which six have been detected in the skin: trichodysplasia spinulosa-associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13 (Table S1; see Supporting Information).

HPyVs share high sequence similarity in the coding region, but the noncoding region, which includes the origin of replication and transcription control sequences for the early and late genes, is highly variable. All HPyVs encode the large T antigen (LT) and small T antigen (sT), which are multifunctional proteins expressed during the early stage of viral replication. Figures 1 and 2 give schematic representations of each cutaneous HPyV genome. The presence of HPyVs can be detected in skin biopsies using qualitative and quantitative polymerase chain reaction (PCR) analyses, but presently only for research purposes.[11,12]

Figure 1.

Schematic representation of Merkel cell polyomavirus (MCPyV), human polyomavirus (HPyV)6, HPyV7 and trichodysplasia spinulosa-associated polyomavirus (TSPyV). Coloured arrows indicate gene products and their approximate locations. The early region encodes for the various T antigens, while the late region encodes for the capsid proteins viral protein (VP)1, VP2 and VP3. ALTO, alternative T antigen; LT, large T antigen; mT, middle T antigen; sT, small T antigen.

Figure 2.

Schematic representation of human polyomavirus (HPyV)9, HPyV10 and HPyV13. Coloured arrows indicate gene products and their approximate locations. The early region encodes for the various T antigens, while the late region encodes for the capsid proteins viral protein (VP)1, VP2 and VP3. ALTO, alternative T antigen; LT, large T antigen; NCCR, noncoding control region; sT, small T antigen.

Polyomaviruses are thought to have the ability to infect the skin latently without causing clinical symptoms until the host falls into an immunosuppressed state, at which time the virus is believed to reactivate.[13] In this brief review, we provide an update on viral biology, clinical features and targeted therapies for HPyVs of the skin.

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