Variant Analysis of the Thymidine Kinase and DNA Polymerase Genes of Herpes Simplex Virus in Korea: Frequency of Acyclovir Resistance Mutations

Viruses. 2023 Aug 9;15(8):1709. doi: 10.3390/v15081709.

Abstract

The thymidine kinase (TK) and DNA polymerase (pol) genes of the herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are two important genes involved in antiviral resistance. We investigated the genetic polymorphisms of the HSV-TK and pol genes in clinical isolates from Korean HSV-infected patients using next-generation sequencing (NGS) for the first time in Korea. A total of 81 HSV-1 and 47 HSV-2 isolates were examined. NGS was used to amplify and sequence the TK and pol genes. Among the 81 HSV-1 isolates, 12 and 17 natural polymorphisms and 9 and 23 polymorphisms of unknown significance in TK and pol were found, respectively. Two HSV-1 isolates (2.5%) exhibited the E257K amino acid substitution in TK, associated with antiviral resistance. Out of 47 HSV-2 isolates, 8 natural polymorphisms were identified in TK, and 9 in pol, with 13 polymorphisms of unknown significance in TK and 10 in pol. No known resistance-related mutations were observed in HSV-2. These findings contribute to our understanding of the genetic variants associated with antiviral resistance in HSV-1 and HSV-2 in Korea, with frequencies of known antiviral resistance-related mutations of 2.5% and 0% in HSV-1 and HSV-2, respectively.

Keywords: HSV-1; HSV-2; antiviral resistance; next-generation sequencing; polymorphisms; variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / pharmacology
  • Antiviral Agents / pharmacology
  • DNA-Directed DNA Polymerase* / genetics
  • Drug Resistance, Viral
  • Herpesvirus 1, Human* / drug effects
  • Herpesvirus 1, Human* / genetics
  • Herpesvirus 2, Human / genetics
  • Humans
  • Mutation
  • Republic of Korea / epidemiology
  • Thymidine Kinase* / genetics

Substances

  • Acyclovir
  • Antiviral Agents
  • DNA-Directed DNA Polymerase
  • Thymidine Kinase

Grants and funding

This research was funded by the Hallym University Research Fund 2017 (HURF-2017-31) and the National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT) (No. 2017R1C1B5017197).