Functional analysis of trichodysplasia spinulosa-associated polyomavirus-encoded large T antigen

Abstract

Trichodysplasia spinulosa-associated polyomavirus (TSPyV or human polyomavirus 8) was identified from patients with trichodysplasia spinulosa, a rare skin disease affecting the faces of immunocompromised patients. Like other polyomaviruses, the TSPyV genome encodes a large T antigen (LT). However, the expression and functions of TSPyV LT in infected cells remain largely unknown. In the present study, we cloned a full-length TSPyV LT cDNA from cells transfected with the full-length of TSPyV LT DNA. Transfection study using green fluorescence protein-tagged LT expression plasmids showed that TSPyV LT was expressed in the nucleus of transfected cells. Analysis of deletion mutants identified a nuclear localization signal in TSPyV LT. Recombinant TSPyV LT exhibited an ATPase activity. TSPyV LT has a chitinase-like domain; however, no chitinase activity was detected. Immunoprecipitation assays revealed that TSPyV LT bound to retinoblastoma 1, but not to p53 in transfected cells. Expression of TSPyV LT in NIH3T3 cells induced colony formation in soft agar, suggesting its transformation activity. These data indicate that TSPyV LT may be associated with the pathogenesis of trichodysplasia spinulosa, which is a hyperplasia of keratinocytes in inner hair follicles.