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G. M. Verjans, R. Duan, R. D. de Vries, F. B. van Loenen, L. Remeijer, A. D. M. E. Osterhaus; Acyclovir Sensitivity and Genetic Characteristics of Sequential Herpes Simplex Virus Type 1 Corneal Isolates From Patients With Recurrent Herpetic Keratitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):840.
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Successive acyclovir (ACV) treatment of patients with recurrent herpes simplex virus type 1 (HSV-1) keratitis (rHK) may induce ACV resistance. To understand the incidence and clinical significance of ACV resistance in rHK, the ACV sensitivities and genetic characteristics of sequential corneal HSV-1 isolates was analyzed.
Sequential corneal HSV-1 isolates from 15 immunecompetent rHK patients were assayed for ACV sensitivity and genotyped by analyzing the hypervariable regions of the HSV-1 genes US1, US4, US7 and US12. Thymidine kinase (TK) gene of each isolate was sequenced and the proportion of ACV resistant (ACVR) variants within selected isolates determined.
ACV sensitivity patterns differed between sequential isolates of 8 of 15 patients. Whereas the sequential isolates of 6 of these 8 individuals had the same patient-specific HSV-1 genotype, the respective paired isolates’ TK sequences were generally different. The TK mutations correlated with the isolates’ in vitro ACVR phenotype and the patients’ unresponsiveness to ACV therapy at time of sampling.
Cornea HSV-1 isolates are mixtures of ACV susceptible and resistant variants commonly sharing the same genotype but divergent in their TK sequences. The reappearance of the same ACVR HSV-1 variant during a successive rHK episode suggests reactivation of the respective ACVR variant from their latency stronghold.
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