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.
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.
Morfin
F
F
Laboratory of Virology, Hospices Civils de Lyon, Lyon, France. fmorfin@rockefeller.univ-lyon1.fr
Thouvenot
D
D
Aymard
M
M
Souillet
G
G
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
D000998:Antiviral Agents; D013937:Thymidine Kinase; D000212:Acyclovir