Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate

J Infect Dis. 2000 Apr;181(4):1458-61. doi: 10.1086/315387. Epub 2000 Apr 13.


Acyclovir resistance is not a recognized problem among neonates with perinatal herpes simplex virus (HSV) infection. A premature newborn with neurocutaneous HSV infection was treated for 21 days with acyclovir. Disseminated disease recurred 8 days later. A recurrent isolate was resistant to acyclovir and lacked thymidine kinase activity on the basis of a frameshift mutation in the thymidine kinase (tk) gene. Compared with the sensitive isolate obtained during primary infection, replication of the resistant isolate was reduced on primary and permanent cells and even further impaired on cells deleted for cellular tk. The resistant isolate lacked virulence in a murine model of genital infection. Acyclovir-resistant HSV-2 mutants can develop rapidly in neonatal infection and cause clinically significant disease, despite decreased replication in vitro and attenuated virulence in an animal model.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyclovir / therapeutic use*
  • Adult
  • Animals
  • Antiviral Agents / therapeutic use*
  • Chlorocebus aethiops
  • Cricetinae
  • Drug Resistance, Microbial
  • Fatal Outcome
  • Female
  • Herpesvirus 2, Human* / enzymology
  • Herpesvirus 2, Human* / genetics
  • Herpesvirus 2, Human* / physiology
  • Humans
  • Infant, Newborn
  • Male
  • Mice
  • Mutation
  • Thymidine Kinase / genetics
  • Tumor Cells, Cultured
  • Vero Cells
  • Virus Replication


  • Antiviral Agents
  • Thymidine Kinase
  • Acyclovir