Common and new acyclovir resistant herpes simplex virus-1 mutants causing bilateral recurrent herpetic keratitis in an immunocompetent patient

J Infect Dis. 2014 Feb 1;209(3):345-9. doi: 10.1093/infdis/jit437. Epub 2013 Aug 14.

Abstract

We investigated thymidine kinase (tk) mutants isolated during multiple episodes of recurrent bilateral acyclovir resistant herpes simplex keratitis in an immunocompetent patient. From one eye, we found a single guanine insertion, previously shown to greatly reduce TK expression, and from the other, a previously unidentified substitution, which genetic experiments confirmed confers drug resistance. The substitution, although distant from substrate binding sites, reduced thymidine phosphorylation 10-20-fold, and acyclovir phosphorylation >100-fold. This phenotype should permit reactivation from latency to cause recurrent disease. The results may have implications for the prevalence and prevention of acyclovir resistance in patients with herpes simplex keratitis.

Keywords: acyclovir; antiviral drug resistance; herpes simplex keratitits; herpes simplex virus; thymidine kinase.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyclovir / pharmacology*
  • Adult
  • Amino Acid Substitution
  • Antiviral Agents / pharmacology*
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Drug Resistance, Viral*
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / isolation & purification
  • Humans
  • Keratitis, Herpetic / virology*
  • Male
  • Molecular Sequence Data
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation, Missense
  • Phosphorylation
  • Point Mutation
  • Recurrence
  • Sequence Analysis, DNA
  • Thymidine / metabolism
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • DNA, Viral
  • Mutant Proteins
  • Viral Proteins
  • Thymidine Kinase
  • Thymidine
  • Acyclovir

Associated data

  • GENBANK/KC881056