Reactivation of acyclovir-resistant thymidine kinase-deficient herpes simplex virus harbouring single base insertion within a 7 gs homopolymer repeatof the thymidine kinase gene

HSV infections are treated efficiently and prevented by acyclovir, although resistant strains have been reported. Resistance to acyclovir involves mai nly mutations in the viral gene encoding thymidine kinase; mutations may le ad to an altered or, more frequently, deficient TK. These acyclovir-resista nt TK deficient strains are not able to reactivate from a latent infection in an experimental model, compared to TK positive strains. A case is report ed of a bone marrow transplant child who developed HSV infection at 11 days post-transplantation. Acyclovir-resistant HSV 1 was isolated on day 19 pos t-transplantation. The patient was cured of his infection. A resistant viru s was detected 20 months later that harboured the same TK gene mutation as the first resistant virus. This mutation is an insertion of one guanine in a homopolymer repeat of seven guanines located at codon 146 of TK. It has p reviously been reported and associated with the expression of a deficient T K activity and the ability to reactivate in mice. These results corroborate the clinical relevance of this mutation, which is associated with acyclovi r-resistant recurrent infections in humans. (C) 2000 Wiley-Liss, Inc.