ArticleAntimicrobial agents and chemotherapy2010
Genotypic characterization of UL23 thymidine kinase and UL30 DNA polymerase of clinical isolates of herpes simplex virus: natural polymorphism and mutations associated with resistance to antivirals.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 134 citations in OpenAlex.
- Genotypic Characterization of Herpes Simplex Virus Type 1 Isolates in Immunocompromised Patients in Rio de Janeiro, Brazil.PloS one · 2015Trial
- Clinical and genotypic characteristics of antiviral-resistant herpes simplex virus 1 and 2 infections: a case series.BMC infectious diseases · 2026Observational
- Unveiling the prevalence of sexually transmitted infections and its etiology among married women of remote South Andaman Island in India.Scientific reports · 2026Article
- Survey of Haemosporidian Parasites in Wild Stone-Curlews (Animals : an open access journal from MDPI · 2025Article
- Epidemiological, serological, and viral genomic analysis of an outbreak of elephant hemorrhagic disease in Switzerland.PloS one · 2025Article
- The immunobiology of corneal HSV-1 infection and herpetic stromal keratitis.Clinical microbiology reviews · 2024Review
- Embracing Complexity: What Novel Sequencing Methods Are Teaching Us About Herpesvirus Genomic Diversity.Annual review of virology · 2024Review
- Combination of ganciclovir and trifluridine prevents drug-resistance emergence in HSV-1.Antimicrobial agents and chemotherapy · 2024Article
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- Diagnostic performance of real-time quantitative PCR in tear samples in various subtypes of herpes simplex keratitis.Journal of clinical microbiology · 2023Article
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- Novel mutations in antiviral multiresistant HSV-2 genital lesion: A case report.Journal of medical virology · 2022Article
- Phylogeographic analysis reveals an ancient East African origin of human herpes simplex virus 2 dispersal out-of-Africa.Nature communications · 2022Article
- Targeting m6A modification inhibits herpes virus 1 infection.Genes & diseases · 2022Article
- 40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?International journal of molecular sciences · 2022Review
- Non-cytopathic herpes simplex virus type-1 isolated from acyclovir-treated patients with recurrent infections.Scientific reports · 2022Article
- Herpes simplex virus 2 (HSV-2) evolves faster in cell culture than HSV-1 by generating greater genetic diversity.PLoS pathogens · 2021Article
- Hsp90 Inhibitors Prevent HSV-1 Replication by Directly Targeting UL42-Hsp90 Complex.Frontiers in microbiology · 2021Article
- Alphaherpesvirus Genomics: Past, Present and Future.Current issues in molecular biology · 2021Review
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanisms of herpes simplex virus (HSV) resistance to antiviral drugs interfering with viral DNA synthesis reported so far rely on the presence of mutations within UL23 (thymidine kinase [TK]) and UL30 (DNA polymerase) genes. The interpretation of genotypic antiviral resistance assay results requires the clear distinction between resistance mutations and natural interstrain sequence variations. The objectives of this work were to describe extensively the natural polymorphism of UL23 TK and UL30 DNA polymerase among HSV-1 and HSV-2 strains and the amino acid changes potentially associated with HSV resistance to antivirals. The sequence analysis of the full-length UL23 and UL30 genes was performed. Ninety-four drug-sensitive clinical isolates (43 HSV-1 and 51 HSV-2) and 3 laboratory strains (KOS, gHSV-2, and MS2) were studied for natural polymorphism, and 25 clinical isolates exhibiting phenotypic traits of resistance to antivirals were analyzed for drug resistance mutations. Our results showed that TK and DNA polymerase are highly conserved among HSV strains, with a weaker variability for HSV-2 strains. This study provided a precise map of the natural polymorphism of both viral enzymes among HSV-1 and HSV-2 isolates, with the identification of 15 and 51 polymorphisms never previously described for TK and DNA polymerase, respectively, which will facilitate the interpretation of genotypic antiviral-resistant testing. Moreover, the genotypic characterization of 25 drug-resistant HSV isolates revealed 8 new amino acid changes located in TK and potentially accounting for acyclovir (ACV) resistance.
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