Database on natural polymorphisms and resistance-related non-synonymous mutations in thymidine kinase and DNA polymerase genes of herpes simplex virus types 1 and 2

J Antimicrob Chemother. 2016 Jan;71(1):6-16. doi: 10.1093/jac/dkv285. Epub 2015 Oct 3.

Abstract

The use of genotypic resistance testing of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) is increasing because the rapid availability of results significantly improves the treatment of severe infections, especially in immunocompromised patients. However, an essential precondition is a broad knowledge of natural polymorphisms and resistance-associated mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes, of which the DNA polymerase (Pol) enzyme is targeted by the highly effective antiviral drugs in clinical use. Thus, this review presents a database of all non-synonymous mutations of TK and DNA pol genes of HSV-1 and HSV-2 whose association with resistance or natural gene polymorphism has been clarified by phenotypic and/or functional assays. In addition, the laboratory methods for verifying natural polymorphisms or resistance mutations are summarized. This database can help considerably to facilitate the interpretation of genotypic resistance findings in clinical HSV-1 and HSV-2 strains.

Publication types

  • Review

MeSH terms

  • DNA-Directed DNA Polymerase / genetics*
  • Drug Resistance, Viral*
  • Genotype
  • Humans
  • Mutation, Missense*
  • Polymorphism, Genetic*
  • Simplexvirus / drug effects*
  • Simplexvirus / enzymology*
  • Simplexvirus / genetics
  • Thymidine Kinase / genetics*

Substances

  • Thymidine Kinase
  • DNA-Directed DNA Polymerase