ArticleAntimicrobial agents and chemotherapy2015
Drug resistance of clinical varicella-zoster virus strains confirmed by recombinant thymidine kinase expression and by targeted resistance mutagenesis of a cloned wild-type isolate.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Nanomedicine against antimicrobial resistance: mechanistic insights and next-generation therapeutic potential.Frontiers in chemistry · 2026Review
- Small Molecule Compounds Inhibit Varicella-Zoster Virus Replication by Targeting the Portal Protein-Capsid Interface.Viruses · 2025Article
- Review
- Characteristics of Helicase-Primase Inhibitor Amenamevir-Resistant Herpes Simplex Virus.Antimicrobial agents and chemotherapy · 2021Article
- [S2k guideline for the diagnosis and therapy of zoster and post-zoster neuralgia].GMS infectious diseases · 2020Article
- Role of the JNK Pathway in Varicella-Zoster Virus Lytic Infection and Reactivation.Journal of virology · 2017Article
- Clinical and biological insights from viral genome sequencing.Nature reviews. Microbiology · 2017Review
- Recombinant herpes simplex virus type 1 strains with targeted mutations relevant for aciclovir susceptibility.Scientific reports · 2016Article
- Diagnosis, antiviral therapy, and prophylaxis of varicella-zoster virus infections.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2016Review
- The population genetics of drug resistance evolution in natural populations of viral, bacterial and eukaryotic pathogens.Molecular ecology · 2016Review
- Varicella-zoster virus infections - antiviral therapy and diagnosis.GMS infectious diseases · 2016Review
- Sequence Analysis of Herpes Simplex Virus 1 Thymidine Kinase and DNA Polymerase Genes from over 300 Clinical Isolates from 1973 to 2014 Finds Novel Mutations That May Be Relevant for Development of Antiviral Resistance.Antimicrobial agents and chemotherapy · 2015Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, approaches were developed to examine the phenotypes of nonviable clinical varicella-zoster virus (VZV) strains with amino acid substitutions in the thymidine kinase (TK) (open reading frame 36 [ORF36]) and/or DNA polymerase (Pol) (ORF28) suspected to cause resistance to antivirals. Initially, recombinant TK proteins containing amino acid substitutions described as known or suspected causes of antiviral resistance were analyzed by measuring the TK activity by applying a modified commercial enzyme immunoassay. To examine the effects of these TK and Pol substitutions on the replication of recombinant virus strains, the method of en passant mutagenesis was used. Targeted mutations within ORF36 and/or ORF28 and an autonomously expressed gene of the monomeric red fluorescent protein for plaque identification were introduced into the European wild-type VZV strain HJO. Plaque reduction assays revealed that the amino acid substitutions with unknown functions in TK, Q303stop, N334stop, A163stop, and the deletion of amino acids 7 to 74 aa (Δaa 7 to 74), were associated with resistance against acyclovir (ACV), penciclovir, or brivudine, whereas the L73I substitution and the Pol substitutions T237K and A955T revealed sensitive viral phenotypes. The results were confirmed by quantitative PCR by measuring the viral load under increasing ACV concentrations. In conclusion, analyzing the enzymatic activities of recombinant TK proteins represent a useful tool for evaluating the significance of amino acid substitutions in the antiviral resistance of clinical VZV strains. However, direct testing of replication-competent viruses by the introduction of nonsynonymous mutations in a VZV bacterial artificial chromosome using en passant mutagenesis led to reliable phenotypic characterization results.
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