The transmembrane channel-like protein family and human papillomaviruses Insights into epidermodysplasia verruciformis and progression to squamous cell carcinoma

Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by increased sensitivity to infection by the beta-subtype of human papillomaviruses (beta-HPVs), causing persistent, tinea versicolor-like dermal lesions. In a majority of affected individuals, these macular lesions progress to invasive cutaneous squamous cell carcinoma (CSCC) in sun-exposed areas. While mutations in transmembrane channel-like 6 (TMC6/EVER1) and 8 (TMC8/EVER2) have been causally linked to EV, their molecular functions are unclear. It is likely that their protective effects involve regulation of the beta-HPV life cycle, host keratinocyte apoptosis vs. survival balance and/or T-cell interaction with infected host cells.