title: Acyclovir-resistant herpes simplex virus type 1 in intra-ocular fluid samples of herpetic uveitis patients.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Viroscience Lab, Erasmus MC, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: van Velzen
authors.forename: Tom
authors.initials: T
authors.lastname: Missotten
authors.forename: Freek B
authors.initials: FB
authors.lastname: van Loenen
authors.forename: Roland J W
authors.initials: RJ
authors.lastname: Meesters
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
authors.forename: G Seerp
authors.initials: GS
authors.lastname: Baarsma
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Georges M G M
authors.initials: GM
authors.lastname: Verjans
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology*; D001082:Aqueous Humor / Q000821:virology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D013937:Thymidine Kinase / Q000235:genetics; D014605:Uveitis / Q000821:virology*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D013937:Thymidine Kinase; D000212:Acyclovir