Acyclovir Susceptibility and Genetic Characteristics of Sequential Herpes Simplex Virus Type 1 Corneal Isolates from Patients with Recurrent Herpetic Keratitis
| العنوان: | Acyclovir Susceptibility and Genetic Characteristics of Sequential Herpes Simplex Virus Type 1 Corneal Isolates from Patients with Recurrent Herpetic Keratitis |
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| المؤلفون: | Jessica M. van Dun, Rui Duan, Albert D. M. E. Osterhaus, Freek B. van Loenen, Georges M. G. M. Verjans, Lies Remeijer, Rory D. de Vries |
| المساهمون: | Virology |
| المصدر: | Journal of Infectious Diseases, 200(9), 1402-1414. Oxford University Press |
| بيانات النشر: | Oxford University Press, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adult, Male, viruses, Acyclovir, Herpesvirus 1, Human, Biology, medicine.disease_cause, Antiviral Agents, Herpesviridae, Virus, Keratitis, Alphaherpesvirinae, Drug Resistance, Viral, Genotype, Virus latency, medicine, Humans, Immunology and Allergy, heterocyclic compounds, Prospective Studies, Aciclovir, Aged, virus diseases, Middle Aged, biochemical phenomena, metabolism, and nutrition, medicine.disease, biology.organism_classification, Virology, Virus Latency, Infectious Diseases, Herpes simplex virus, Keratitis, Herpetic, medicine.drug |
| الوصف: | Background: The incidence and clinical significance of herpes simplex virus type 1 (HSV-1) acyclovir resistance were determined in patients with recurrent herpetic keratitis (RHK). Methods: Sequential corneal isolates (np39) from 15 immunocompetent patients with RHK were assayed for acyclovir susceptibility and genotyped by analyzing the hypervariable regions of the HSV-1 genes US1 and US12. The thymidine kinase (TK) gene of each isolate was sequenced, and the proportion of acyclovir-resistant viruses within isolates was determined. Results: Uniform acyclovir-resistant or acyclovir-sensitive sequential isolates were identified in 4 and 2 patients, respectively. Notably, the acyclovir susceptibility of sequential isolates changed from acyclovir sensitive to acyclovir resistant (5 patients) or from acyclovir resistant to acyclovir sensitive (3 patients). The acyclovir-resistant phenotype of the isolates correlated with the patients unresponsiveness to acyclovir therapy. Combined analyses of the TK gene and genotype of sequential isolates showed that acyclovir-sensitive isolates contained multiple acyclovirresistant variants of the same virus and that an identical acyclovir-resistant HSV-1 strain reappeared in the patients cornea during RHK episodes. Conclusions: Corneal HSV-1 isolates are mixtures of acyclovir-sensitive and acyclovir-resistant viruses that share the same genotype but have different TK sequences. Recovery of the same acyclovir-resistant virus during consecutive herpetic keratitis episodes suggests that acyclovir-resistant HSV-1 establishes latency and reactivates intermittently to cause acyclovir-refractory RHK. 2009 by the Infectious Diseases Society of America. |
| تدمد: | 1537-6613 0022-1899 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1ed3d83cc687213eccbdd825a07103d5Test https://doi.org/10.1086/606028Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1ed3d83cc687213eccbdd825a07103d5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15376613 00221899 |
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