The herpes simplex virus-induced demise of keratinocytes is associated with a dysregulated pattern of p63 expression

p63 plays a pivotal role in the development and maintenance of stratified epithelial tissues. In an effort to gain insight into the pathogenic mechanisms of skin infections caused by HSV-1 and HSV-2, we determined the patterns of p63 expression in primary keratinocytes and in the HaCaT cell line. The levels of ΔNp63α and a 50 kDa p73 isoform were decreased, Bax-α remained unaffected, while the expressions of the Bax-β, TAp63γ and a 44.5 kDa p73 isoform were highly increased in both HSV-1-infected HaCaT cells and primary keratinocytes. In contrast, in response to HSV-2 infection the levels of ΔNp63α, a 50 kDa p73 isoform and a 44.5 kDa p73 protein were decreased, Bax-α and TAp63γ remained unaffected, while the expression of Bax-β was slightly increased. The knockdown of TAp63 expression enhanced the viability of HSV-1-infected cells. Thus, HSV-1 and HSV-2 modulate the patterns of p63 and Bax expression in a serotype-specific manner. The dysregulated pattern of p63 expression observed in HSV-infected keratinocytes may comprise part of a mechanism by which these viruses perturb the functions of keratinocytes and lead to their demise.