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Human polyomavirus 7 ( HP yV7)‐associated dermatoses: novel molecular mechanism driven by viral activation of 4E‐ BP 1 and MEK ‐ ERK ‐ cJ un
Author(s) -
Wu Julie H.,
Narayanan Deepika,
Simonette Rebecca A.,
Rady Peter L.,
Tyring Stephen K.
Publication year - 2019
Publication title -
international journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 93
eISSN - 1365-4632
pISSN - 0011-9059
DOI - 10.1111/ijd.14315
Subject(s) - keratinocyte , pathogenesis , antigen , merkel cell polyomavirus , mapk/erk pathway , biology , immunology , phosphorylation , microbiology and biotechnology , cell culture , carcinoma , genetics , merkel cell carcinoma
A number of pruritic skin conditions arising in immunocompromised patients are associated with viral infection. Recently, human polyomavirus 7 ( HP yV7) has been implicated in the pathogenesis of eruptive pruritic parakeratotic and dyskeratotic dermatoses with distinct “peacock plumage” histology. While expression of HP yV7 viral protein, namely small tumor ( sT ) antigen, is prominent within lesional tissue, the functional role of HP yV7 in cutaneous pathobiology is not yet known. In this study, we demonstrate a novel role for HP yV7 sT antigen in pathways important for the maintenance of keratinocyte structure and function. In particular, HP yV7 sT was found to dysregulate protein phosphatase 2A through physical interactions that led to activation of MEK / ERK /c‐Jun and 4E‐ BP 1 (proteins that contribute to disorganized keratinocyte growth as well as hyperproliferative and inflammatory states). Given that HP yV7 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 HP yV7 in cutaneous disease.