Egress-enhancing mutation reveals the inefficiency of non-enveloped virus cell exit.

ABSTRACT: Viruses encounter a range of selective pressures, but inefficiencies during replication can be masked. To uncover factors that limit viral replication, we used forward genetics to enrich for a murine norovirus (MNV) mutant with faster replication. We sequentially harvested the earliest progeny in cultured cells and identified a single amino acid change in the viral NS3 protein, K40R, that was sufficient to enhance replication speed. We found that the NS3-K40R virus induced earlier cell death and viral egress compared with wild-type virus. Mechanistically, NS3-K40R protein disrupted membranes more efficiently than wild-type NS3 protein, potentially contributing to increased mitochondrial dysfunction and cell death. Immunodeficient mice infected with NS3-K40R virus had increased titers, sugg

SUBMITTER: Rodriguez-Irizarry VJ 

PROVIDER: S-EPMC12212872 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature