LB1019 The early region of trichodysplasia spinulosa polyomavirus drives proliferation, altered differentiation, and ectopic expression of hair follicle differentiation markers in interfollicular tail epidermis

Trichodysplasia spinulosa (TS) is a rare hair follicle disorder that develops in immunosuppressed patients and associated with productive infection by the TSPyV polyomavirus. Affected follicles contain an attenuated matrix, expanded compartment of aberrantly proliferating inner root sheath (IRS)-like cells containing viral particles, disorganized mass shaft-like cells. The expression early region (ER) genes encoding T antigens (TAgs) drive cellular proliferation genome replication tightly restricted to matrix IRS-like To probe potential impact TAg on other aspects epithelial biology, we generated bitransgenic iK5;TSER mice harboring Cre-inducible ER could be activated K5-expressing their progeny using tamoxifen. As previously described, TAgs skin adult led development numerous dysmorphic follicles. Additionally, interfollicular tail epidermis was hyperplastic contained small collections TAg+ cells, some which were multinucleated, clear cytoplasm. Many these (Ki67+) strikingly deficient epidermal keratins (K5, K14, K1, K10). Remarkably, subset aberrant ectopically expressed IRS marker trichohyalin hair-specific keratin. Our findings suggest addition primary function driving cell cycle progression needed for replication, may also contribute human pathology modulating differentiation status target