title: 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.
abstract: BACKGROUND
  Acyclovir-resistant herpes simplex viruses (HSV) are commonly recovered from immunocompromised individuals who exhibit chronic and/or disseminated herpetic lesions.
  
  
  OBJECTIVE
  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.
authors.affiliation: Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Quebec, CHUQ-CHUL, and Laval University, Québec City, Que., Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Lebel
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000494:pharmacology*; D000287:Administration, Topical; D019943:Amino Acid Substitution; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D024882:Drug Resistance, Viral; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D020125:Mutation, Missense; D013937:Thymidine Kinase / Q000235:genetics; D014774:Virulence
chemical_list: D000998:Antiviral Agents; D013937:Thymidine Kinase; D000212:Acyclovir