Viral fitness of MHV-68 viruses harboring drug resistance mutations in the protein kinase or thymidine kinase.

Viral fitness of MHV-68 viruses harboring drug resistance mutations in the protein kinase or thymidine kinase. Antiviral Res. 2020 Aug 04;:104901 Authors: Trompet E, Topalis D, Gillemot S, Snoeck R, Andrei G Abstract Murine γ-herpesvirus-68 (MHV-68), genetically and biologically related to human γ-herpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, can be easily propagated in vitro allowing drug resistance studies. Previously, we described specific changes in MHV-68 protein kinase (PK) and thymidine kinase (TK) associated with resistance to various purine and pyrimidine nucleoside analogues, respectively. To investigate how specific TK and PK mutations affect viral replication capacity, we performed dual infection competition assays in which wild-type and drug-resistant virus compete in absence or presence of antivirals in Vero cells. The composition of the mixed viral population was analyzed using next-generation sequencing and relative fitness of seven MHV-68 PK or TK mutants was calculated based on the frequency of viral variants at the time of infection and after 5-days growth. A MHV-68 mutant losing the PK function due to a 2-nucleotide deletion was less fit than the wild-type virus in absence of antivirals, consistent with the essential role of viral PKs during lytic replication, but overgrew the wild-type virus under pressure of purine nucleosides. TK mutant viruses, with frameshift or missense muta...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research