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Genotypic characterization of the DNA polymerase and sensitivity to antiviral compounds of foscarnet-resistant herpes simplex virus type 1 (HSV-1) derived from a foscarnet-sensitive HSV-1 strain.

ABSTRACT: Foscarnet is widely used for the treatment of acyclovir-resistant herpesvirus infections, and foscarnet-resistant herpesvirus infections are a serious concern in immunocompromised patients. Twenty-seven single-plaque isolates of herpes simplex virus type 1 (HSV-1) resistant to foscarnet were selected from foscarnet- and acyclovir-sensitive HSV-1 strain TAS by exposure to foscarnet, and the DNA polymerase genes were analyzed. The sensitivities of these mutants to foscarnet, cidofovir, S2242, acyclovir, ganciclovir, and penciclovir were determined. A single amino acid substitution, double amino acid substitutions, and a combination of a single amino acid substitution with a deletion or insertion of amino acid residues in the viral DNA polymerase were demonstrated in 21, 4, and 2 isolates, respectively. Of the 27 isolates, an amino acid substitution of serine for asparagine at amino acid position 724 in the DNA polymerase (724 S-N) was detected in 8 isolates. An amino acid substitution in conserved region II was demonstrated in these eight isolates as well as four other isolates. The mutation in the DNA polymerase responsible for resistance to foscarnet was located between the pre-IV region and conserved region V, especially within conserved region II. All the isolates were sensitive or hypersensitive to cidofovir and ganciclovir. Seven, 5, and 15 of the 27 isolates were also sensitive to S2242, acyclovir, and penciclovir, respectively. Thus, most of the foscarnet-resistant HSV-1 isolates were sensitive or hypersensitive to cidofovir and ganciclovir.

SUBMITTER: Saijo M

PROVIDER: S-EPMC547286 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

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Genotypic characterization of the DNA polymerase and sensitivity to antiviral compounds of foscarnet-resistant herpes simplex virus type 1 (HSV-1) derived from a foscarnet-sensitive HSV-1 strain.

Saijo Masayuki M Suzutani Tatsuo T Morikawa Shigeru S Kurane Ichiro I

Antimicrobial agents and chemotherapy 20050201 2

Foscarnet is widely used for the treatment of acyclovir-resistant herpesvirus infections, and foscarnet-resistant herpesvirus infections are a serious concern in immunocompromised patients. Twenty-seven single-plaque isolates of herpes simplex virus type 1 (HSV-1) resistant to foscarnet were selected from foscarnet- and acyclovir-sensitive HSV-1 strain TAS by exposure to foscarnet, and the DNA polymerase genes were analyzed. The sensitivities of these mutants to foscarnet, cidofovir, S2242, acyc ...[more]

PMID: 15673740

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Project description:Topic: Herpes simplex virus (HSV) and varicella zoster virus (VZV) are the most common ocular pathogens associated with infectious anterior uveitis. Currently, there are a number of antiviral agents administered to treat viral anterior uveitis (VAU). However, there is no consensus or guidelines about the most appropriate approach leading for the best treatment outcomes with fewer ocular complications. Clinical Relevance: To perform a systematic review and meta-analysis of the efficacy of different antiviral therapies in the management of anterior uveitis secondary to HSV and VZV. Methods: We searched PubMed, Web of Science, CINAHL, OVID, and Embase up to January 2020. Randomized trials, non-randomized intervention studies, controlled before and after studies and observational studies assessing the effect of oral and or topical treatments for VAU were considered. Data extraction and analysis with evaluation of the risk of bias in the included trials were performed. Results: Oral acyclovir demonstrated a statistically significant good treatment outcome in the management of VZV anterior uveitis (vs. placebo) (OR 0.26, 95% CI 0.11-0.59), but did not have similar effect in HSV anterior uveitis (OR 0.47, 95% CI 0.15-1.50). In the treatment of VZV anterior uveitis, there was significant superiority of oral acyclovir-7 day course-over topical acyclovir (OR 4.17, 95% CI 1.28-13.52). Whereas, there was no significant superiority of one of the following treatment regimens over the others: topical acyclovir over topical corticosteroids (OR 1.86, 95% CI 0.67-5.17), and oral acyclovir-7 day course-over oral acyclovir-14 day course-(OR 0.21, 95% CI 0.01-4.50) or oral valaciclovir (OR 1.40, 95% CI 0.48-4.07). Conclusion: Treatment of HSV and VZV anterior uveitis is currently based on individual experiences and limited literature, largely due to weak clinical trial evidence in this regard. Our results highlight the existence of a substantial gap in our evidence base. This finding might contribute to future research studies to ascertain the role of different antiviral therapies in the treatment of VAU. Systematic Review Registration: PROSPERO registration number: CRD420202 00404.

Dataset Information

Genotypic characterization of the DNA polymerase and sensitivity to antiviral compounds of foscarnet-resistant herpes simplex virus type 1 (HSV-1) derived from a foscarnet-sensitive HSV-1 strain.

Publications

Genotypic characterization of the DNA polymerase and sensitivity to antiviral compounds of foscarnet-resistant herpes simplex virus type 1 (HSV-1) derived from a foscarnet-sensitive HSV-1 strain.

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