Egress-enhancing mutation reveals inefficiency of non-enveloped virus cell exit DOI Creative Commons

Valerie J. Rodriguez-Irizarry,

Robert W. Maples, Julie K. Pfeiffer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

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 murine norovirus (MNV) mutant with faster replication. We sequentially harvested the earliest progeny in cultured cells and identified single amino acid change NS3 protein, K40R, was sufficient enhance speed. found NS3-K40R virus induced earlier cell death egress compared wild-type virus. Mechanistically, protein disrupted membranes more efficiently than potentially contributing increased mitochondrial dysfunction death. Mice infected had titers, suggesting increasing did not reduce fitness vivo . Overall, by using genetic approach, previously unknown inefficiency provide new insights into pressures influence evolution.

Language: Английский

Egress-enhancing mutation reveals inefficiency of non-enveloped virus cell exit DOI Creative Commons

Valerie J. Rodriguez-Irizarry,

Robert W. Maples, Julie K. Pfeiffer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

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 murine norovirus (MNV) mutant with faster replication. We sequentially harvested the earliest progeny in cultured cells and identified single amino acid change NS3 protein, K40R, was sufficient enhance speed. found NS3-K40R virus induced earlier cell death egress compared wild-type virus. Mechanistically, protein disrupted membranes more efficiently than potentially contributing increased mitochondrial dysfunction death. Mice infected had titers, suggesting increasing did not reduce fitness vivo . Overall, by using genetic approach, previously unknown inefficiency provide new insights into pressures influence evolution.

Language: Английский

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