Acyclovir-resistant herpes simplex virus type 1 in intra-ocular fluid samples of herpetic uveitis patients

Monique van Velzen, Tom Missotten, Freek B van Loenen, Roland J W Meesters, Theo M Luider, G Seerp Baarsma, Albert D M E Osterhaus, Georges M G M Verjans

Research output: Contribution to journalArticleResearchpeer-review


BACKGROUND: Acyclovir (ACV) is the antiviral drug of choice to treat patients with herpes simplex virus type 1 (HSV-1) uveitis. The prevalence of intra-ocular ACV-resistant (ACV(R)) HSV-1 in herpetic uveitis is unknown and may have clinical consequences. In addition to its predictive value on ACV susceptibility, the polymorphic HSV-1 thymidine kinase (TK) gene facilitates differentiation between HSV-1 strains.

OBJECTIVES: The objective of this study was to determine the genetic composition and ACV susceptibility of the causative virus in intra-ocular fluid samples (IOF) of HSV-1 uveitis patients.

STUDY DESIGN: The intra-ocular HSV-1 pool from 11 HSV-1 uveitis patients was determined by sequencing IOF-derived viral TK genes. The ACV susceptibility profile of the cloned intra-ocular TK variants was defined by mass spectrometry. In addition, the ganciclovir (GCV) susceptibility of the ACV(R) HSV-1 TK variants was defined.

RESULTS: Intra-ocular fluid samples of HSV-1 uveitis patients contain HSV-1 quasispecies, principally consisting of one major and multiple genetically related minor patient-specific TK variants. Four of 10 patients analyzed had an intra-ocular ACV(R) HSV-1 of which 3 were cross-resistant to GCV. The ACV(R) profile of intra-ocular HSV-1 did not correlate with symptomatic ACV treatment.

CONCLUSIONS: Affected eyes of HSV-1 uveitis patients are commonly infected with a patient-specific HSV-1 quasispecies, including one major and multiple genetically related minor variants. A relatively high prevalence of intra-ocular ACV(R) HSV-1, mainly ACV/GCV cross-resistant viruses, was detected in HSV-1 uveitis patients.

Original languageEnglish
Pages (from-to)215-21
Number of pages7
JournalJournal of clinical virology : the official publication of the Pan American Society for Clinical Virology
Issue number3
Publication statusPublished - Jul 2013


  • Acyclovir/pharmacology
  • Adult
  • Aged
  • Antiviral Agents/pharmacology
  • Aqueous Humor/virology
  • DNA, Viral/chemistry
  • Drug Resistance, Viral
  • Female
  • Herpes Simplex/virology
  • Herpesvirus 1, Human/drug effects
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • Thymidine Kinase/genetics
  • Uveitis/virology


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