TY - JOUR
T1 - Acyclovir-resistant herpes simplex virus type 1 in intra-ocular fluid samples of herpetic uveitis patients
AU - Velzen, Monique
AU - Missotten, T
AU - Loenen, Freek
AU - Meesters, Roland
AU - Luider, Theo
AU - Baarsma, Goitzen
AU - Osterhaus, Ab
AU - Verjans, Georges
PY - 2013
Y1 - 2013
N2 - 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 (ACVR) 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 ACVR 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 ACVR HSV-1 of which 3 were cross-resistant to GCV. The ACVR 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 ACVR HSV-1, mainly ACV/GCV cross-resistant viruses, was detected in HSV-1 uveitis patients. (C) 2013 Elsevier B. V. All rights reserved.
AB - 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 (ACVR) 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 ACVR 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 ACVR HSV-1 of which 3 were cross-resistant to GCV. The ACVR 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 ACVR HSV-1, mainly ACV/GCV cross-resistant viruses, was detected in HSV-1 uveitis patients. (C) 2013 Elsevier B. V. All rights reserved.
U2 - 10.1016/j.jcv.2013.03.014
DO - 10.1016/j.jcv.2013.03.014
M3 - Article
C2 - 23582986
SN - 1386-6532
VL - 57
SP - 215
EP - 221
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
IS - 3
ER -