Polyomaviruses of the Skin: Integrating Molecular and Clinical Advances in an Emerging Class of Viruses Jessica C. Sheu1*, Jessica Tran1*, Peter L. Rady2, Harry Dao Jr1 , Stephen K. Tyring2 , Harrison P. Nguyen1,2,3 1Department of Dermatology, Baylor College of Medicine, Houston, TX 2 Department of Dermatology, McGovern Medical School, Houston, TX 3Department of Dermatology, Emory University School of Medicine, Atlanta, GA *Contributed equally to this work British Journal of Dermatology. DOI: 10.111/bjd.17592

Jessica C. Sheu Jessica Tran Dr Harrison P. Nguyen

Introduction What’s already known? Seven human polyomaviruses have been identified in the skin, all of which were discovered within the past ten years. MCPyV, HPyV6, HPyV7, and TSPyV have been definitively associated with skin disorders, while no clear pathogenic role in skin disease has been established for HPyV9, HPyV10, and HPyV13.

Objective The aim of this study is heightened awareness and clinical recognition of human polyomaviruses will lead to increased reports of human polyomavirus-associated diseases and consequently, a more robust understanding of how to diagnose and treat these conditions.

Methods Comprehensive literature reviews were conducted to summarize the known molecular mechanisms, clinical presentation, and targeted therapies of each of the seven cutaneous human polyomaviruses.

Results (1) This brief study, provide an updated review on viral biology, clinical features, and targeted therapies for HPyV of the skin. A summary table of the human polyomaviruses of the skin and the associated disorders is at the next slide.

Results (2) HPyV Targeted Therapies HPyV5 (MCPyV) Radiotherapy, anti-PD1 antibody drugs (avelumab, pembrolizumab, nivolumab) HPyV6/7 No established therapies TSPyV Definitive treatment not identified, immunosupressive therapy recommended HPyV9, 10, 13

Discussion Since the discovery of MCPyV in 2008, research on the HPyV family has expanded rapidly. Nevertheless, a more robust investigation is needed to identify further presentations of pathological cases of HPyV; to characterise the biology of each species of HPyV; and ultimately, in situations where targeting the virus can benefit clinical outcomes, to develop anti-viral and immunogenic therapies for treating HPyV-mediated disease.

Conclusions What does this study add? This review summarises the known viral biology, pathogenic mechanisms, clinical presentations, and viral therapies of the known cutaneous human polyomaviruses. The authors hope this study will increase readers’ knowledge concerning the pathogenesis and management of human polyomaviruses, while also enabling readers to recognise clinical presentations of human polyomaviruses more readily. Lastly, the authors hope to highlight areas of potential investigation that could expand our current knowledge of the role of human polyomaviruses in dermatoses.

Jessica C. Sheu Jessica Tran Dr. Harrison P. Nguyen Dr. Peter L. Rady Authors Dr. Peter L. Rady Dr. Harry Dao, Jr. Dr. Stephen K. Tyring

Corresponding Author: Harrison Nguyen 1 Baylor Plaza Houston, TX Phone: (713) 798-6131 Fax: (713) 798-3252 Email: harrison.p.nguyen@gmail.com

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