title: Reactivation of acyclovir-resistant thymidine kinase-deficient herpes simplex virus harbouring single base insertion within a 7 Gs homopolymer repeat of the thymidine kinase gene.
abstract: HSV infections are treated efficiently and prevented by acyclovir, although resistant strains have been reported. Resistance to acyclovir involves mainly mutations in the viral gene encoding thymidine kinase; mutations may lead to an altered or, more frequently, deficient TK. These acyclovir-resistant TK deficient strains are not able to reactivate from a latent infection in an experimental model, compared to TK positive strains. A case is reported of a bone marrow transplant child who developed HSV infection at 11 days post-transplantation. Acyclovir-resistant HSV 1 was isolated on day 19 post-transplantation. The patient was cured of his infection. A resistant virus 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 previously been reported and associated with the expression of a deficient TK activity and the ability to reactivate in mice. These results corroborate the clinical relevance of this mutation, which is associated with acyclovir-resistant recurrent infections in humans.
authors.affiliation: Laboratory of Virology, Hospices Civils de Lyon, Lyon, France. fmorfin@rockefeller.univ-lyon1.fr
authors.forename: F
authors.initials: F
authors.lastname: Morfin
authors.forename: D
authors.initials: D
authors.lastname: Thouvenot
authors.forename: M
authors.initials: M
authors.lastname: Aymard
authors.forename: G
authors.initials: G
authors.lastname: Souillet
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D004352:Drug Resistance, Microbial; D006561:Herpes Simplex / Q000175:diagnosis / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D009154:Mutation; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014775:Virus Activation
chemical_list: D000998:Antiviral Agents; D013937:Thymidine Kinase; D000212:Acyclovir