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Pathogenicity and response to topical antiviral therapy in a murine model of acyclovir-sensitive and acyclovir-resistant herpes simplex viruses isolated from the same patient.

Author(s): Lebel A, Boivin G

Affiliation(s): Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Quebec, CHUQ-CHUL, and Laval University, Quebec City, Que., Canada.

Publication date & source: 2006-09, J Clin Virol., 37(1):34-7. Epub 2006 Jun 16.

BACKGROUND: Acyclovir-resistant herpes simplex viruses (HSV) are commonly recovered from immunocompromised individuals who exhibit chronic and/or disseminated herpetic lesions. OBJECTIVES AND STUDY DESIGN: The virulence and response to topical acyclovir therapy were evaluated in a mouse model of zosteriform cutaneous HSV infection using two HSV-1 isolates from the same immunocompromised patient (one susceptible and one resistant to acyclovir). RESULTS: The acyclovir-resistant virus, with a Thr63Ile change in the ATP-binding site of the thymidine kinase gene, produced almost as many skin lesions as the wild-type susceptible virus. As expected from in vitro susceptibility data, the herpetic lesions of the mice infected with the drug-resistant virus did not respond to topical acyclovir therapy. CONCLUSIONS: Some thymidine kinase HSV mutants associated with drug resistance may retain their pathogenicity at least in the mouse model described in this study.

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