Subclinical generation of acyclovir-resistant herpes simplex virus with mutation of homopolymeric guanosine strings during acyclovir therapy

Tohru Daikoku, Hidenori Tannai, Mariko Honda, Tomohiko Onoe, Koma Matsuo, Yasuhiko Onoye, Mika Nishizawa, Takashi Kawana, Tomoko Okuda, Tomomi Hasegawa, Kimiyasu Shiraki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: Suppressive therapy in patients with genital herpes has been used in Japan since 2006. Susceptibility and resistance of herpes simplex virus (HSV)-2 to acyclovir were examined in genital isolates from patients receiving suppressive therapy and compared with those from those naïve to acyclovir and receiving episodic treatment with acyclovir. Objective: The aim of this study was to analyze the effect of acyclovir use on the susceptibility to acyclovir and analysis of the thymidine kinase gene by acyclovir treatment. Methods: Genital HSV isolates were obtained from three patients groups. Susceptibility to acyclovir, the frequency of acyclovir-resistant clones and mutations in the thymidine kinase gene of acyclovir-resistant clones were determined. Results: Susceptibility to ACV was significantly higher in isolates from patients receiving suppressive therapy than those naïve to acyclovir and receiving episodic treatment, but the frequencies of resistant clones were similar among the three groups. Mutation in guanosine homopolymeric strings (G-string mutation) was significantly more frequent in clones during episodic treatment and suppressive therapy than clones from patients naïve to ACV. The frequency of G-string mutation was significantly less frequent in isolates from patients naïve to ACV than those experienced ACV therapy. Conclusion: The frequency of acyclovir-resistant mutants was not increased by episodic and suppressive therapy, but exposure to acyclovir significantly generated G-string mutations, possibly induced by acyclovir. Acyclovir therapy had no substantial effects on the susceptibility of HSV-2 or frequency of resistant virus but did generate subclinical G-string mutants in patients' HSV-2.

Original languageEnglish
Pages (from-to)160-165
Number of pages6
JournalJournal of Dermatological Science
Volume82
Issue number3
DOIs
StatePublished - 2016/06/01

Keywords

  • Acyclovir
  • G-string mutation
  • Herpes simplex virus
  • Suppressive therapy
  • Susceptibility
  • Thymidine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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