{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Trompet E"],"funding":["Fonds Wetenschappelijk Onderzoek"],"pagination":["985"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8227558"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(6)"],"pubmed_abstract":["Drug resistance studies on human γ-herpesviruses are hampered by the absence of an in vitro system that allows efficient lytic viral replication. Therefore, we employed murine γ-herpesvirus-68 (MHV-68) that efficiently replicates in vitro as a model to study the antiviral resistance of γ-herpesviruses. In this study, we investigated the mechanism of resistance to nucleoside (ganciclovir (GCV)), nucleotide (cidofovir (CDV), HPMP-5azaC, HPMPO-DAPy) and pyrophosphate (foscarnet (PFA)) analogues and the impact of these drug resistance mutations on viral fitness. Viral fitness was determined by dual infection competition assays, where MHV-68 drug-resistant viral clones competed with the wild-type virus in the absence and presence of antivirals. Using next-generation sequencing, the composition "],"journal":["Viruses"],"pubmed_title":["An MHV-68 Mutator Phenotype Mutant Virus, Confirmed by CRISPR/Cas9-Mediated Gene Editing of the Viral DNA Polymerase Gene, Shows Reduced Viral Fitness."],"pmcid":["PMC8227558"],"funding_grant_id":["1S04516N"],"pubmed_authors":["Trompet E","Andrei G","Topalis D","Temblador A","Snoeck R","Gillemot S"],"additional_accession":[]},"is_claimable":false,"name":"An MHV-68 Mutator Phenotype Mutant Virus, Confirmed by CRISPR/Cas9-Mediated Gene Editing of the Viral DNA Polymerase Gene, Shows Reduced Viral Fitness.","description":"Drug resistance studies on human γ-herpesviruses are hampered by the absence of an in vitro system that allows efficient lytic viral replication. Therefore, we employed murine γ-herpesvirus-68 (MHV-68) that efficiently replicates in vitro as a model to study the antiviral resistance of γ-herpesviruses. In this study, we investigated the mechanism of resistance to nucleoside (ganciclovir (GCV)), nucleotide (cidofovir (CDV), HPMP-5azaC, HPMPO-DAPy) and pyrophosphate (foscarnet (PFA)) analogues and the impact of these drug resistance mutations on viral fitness. Viral fitness was determined by dual infection competition assays, where MHV-68 drug-resistant viral clones competed with the wild-type virus in the absence and presence of antivirals. Using next-generation sequencing, the composition ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2026-04-08T09:10:49.394Z","creation":"2022-02-10T19:51:35.362Z"},"accession":"S-EPMC8227558","cross_references":{"pubmed":["34073189"],"doi":["10.3390/v13060985"]}}