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.
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 uveitispatients. STUDY DESIGN: The intra-ocular HSV-1 pool from 11 HSV-1 uveitispatients 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 uveitispatients 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 uveitispatients 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 uveitispatients.
Authors: Peter J Ireland; John E Tavis; Michael P D'Erasmo; Danielle R Hirsch; Ryan P Murelli; Mark M Cadiz; Bindi S Patel; Ankit K Gupta; Tiffany C Edwards; Maria Korom; Eileen A Moran; Lynda A Morrison Journal: Antimicrob Agents Chemother Date: 2016-03-25 Impact factor: 5.191
Authors: Arif A Khan; Ruchi Srivastava; Doran Spencer; Sumit Garg; Daniel Fremgen; Hawa Vahed; Patricia P Lopes; Thanh T Pham; Charlie Hewett; Jasmine Kuang; Nicolas Ong; Lei Huang; Vanessa M Scarfone; Anthony B Nesburn; Steven L Wechsler; Lbachir BenMohamed Journal: J Virol Date: 2015-01-21 Impact factor: 5.103
Authors: Hancheng Guan; Manunya Nuth; Vivian Lee; Chenyan Lin; Claire H Mitchell; Wennan Lu; Richard W Scott; Michael H Parker; John L Kulp; Allen B Reitz; Robert P Ricciardi Journal: Ocul Surf Date: 2020-11-06 Impact factor: 5.033
Authors: Johanna G Mitterreiter; Maarten J Titulaer; Gijsbert P van Nierop; Jeroen J A van Kampen; Georgina I Aron; Albert D M E Osterhaus; Georges M G M Verjans; Werner J D Ouwendijk Journal: PLoS One Date: 2016-05-12 Impact factor: 3.240