Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate

Acyclovir resistance is not a recognized problem among neonates with perina tal herpes simplex virus (HSV) infection. A premature newborn with neurocut aneous HSV infection was treated for 21 days with acyclovir. Disseminated d isease recurred 8 days later. A recurrent isolate was resistant to acyclovi r and lacked thymidine kinase activity on the basis of a frame-shift mutati on in the thymidine kinase (tk) gene. Compared with the sensitive isolate o btained during primary infection, replication of the resistant isolate was reduced on primary and permanent cells and even further impaired on cells d eleted for cellular tk. The resistant isolate lacked virulence in a murine model of genital infection. Acyclovir-resistant HSV-2 mutants can develop r apidly in neonatal infection and cause clinically significant disease, desp ite decreased replication in vitro and attenuated virulence in an animal mo del.