Selectivity of antiviral effectiveness derived from differences of herpes simplex virus-coded thymidine kinases.

Abstract

Herpes simplex viruses are human pathogens that cause oral and ocular lesions (HSV-1) or genital lesions (HSV-2). These viruses code for enzymes with substrate specificities different from those of the host cell. The pyrimidine metabolism of the cell is augmented by a virus-coded deoxythymidine (dThd) kinase (TK). This enzyme has a relatively broad phosphate acceptor specificity which permits the phosphorylation of several antiviral nucleoside analogs, the first step in their activation. These analogs are selective inhibitors of DNA synthesis in virus-infected cells, in part, because they are phosphorylated to their triphosphate derivatives only in infected cells.