Human polyomavirus 7 ( HP yV7)‐associated dermatoses: novel molecular mechanism driven by viral activation of 4E‐ BP 1 and MEK ‐ ERK ‐ cJ un
- 10 December 2018
- journal article
- research article
- Published by Wiley in International Journal of Dermatology
- Vol. 58 (4), 383-387
- https://doi.org/10.1111/ijd.14315
Abstract
A number of pruritic skin conditions arising in immunocompromised patients are associated with viral infection. Recently, human polyomavirus 7 (HPyV7) has been implicated in the pathogenesis of eruptive pruritic parakeratotic and dyskeratotic dermatoses with distinct “peacock plumage” histology. While expression of HPyV7 viral protein, namely small tumor (sT) antigen, is prominent within lesional tissue, the functional role of HPyV7 in cutaneous pathobiology is not yet known. In this study, we demonstrate a novel role for HPyV7 sT antigen in pathways important for the maintenance of keratinocyte structure and function. In particular, HPyV7 sT was found to dysregulate protein phosphatase 2A through physical interactions that led to activation of MEK/ERK/c‐Jun and 4E‐BP1 (proteins that contribute to disorganized keratinocyte growth as well as hyperproliferative and inflammatory states). Given that HPyV7 actively infects keratinocytes and sT antigen is highly expressed in pruritic dyskeratotic/parakeratotic dermatoses, our data provide important mechanistic evidence supporting a pathogenic role for HPyV7 in cutaneous disease.Keywords
This publication has 20 references indexed in Scilit:
- Human polyomavirus-7–associated eruption successfully treated with acitretinAmerican Journal of Transplantation, 2018
- Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatosesJournal of the American Academy of Dermatology, 2016
- Frequent detection of human polyomavirus 6 in keratoacanthomas.Diagnostic Pathology, 2016
- Molecular insight into the viral biology and clinical features of trichodysplasia spinulosaBritish Journal of Dermatology, 2015
- Presence of Human Polyomavirus 6 in Mutation-Specific BRAF Inhibitor–Induced Epithelial ProliferationsJAMA Dermatology, 2014
- Human Polyomavirus 7-Associated Pruritic Rash and Viremia in Transplant RecipientsThe Journal of Infectious Diseases, 2014
- Identification of a Novel Polyomavirus in a Pancreatic Transplant Recipient With Retinal Blindness and Vasculitic MyopathyThe Journal of Infectious Diseases, 2014
- A cornucopia of human polyomavirusesNature Reviews Microbiology, 2013
- Discovery of a New Human Polyomavirus Associated with Trichodysplasia Spinulosa in an Immunocompromized PatientPLoS Pathogens, 2010
- Clonal Integration of a Polyomavirus in Human Merkel Cell CarcinomaScience, 2008