Tradeoffs in viral fitness driven by alternative entry pathways.

ABSTRACT: Enveloped viruses can enter cells either through endocytosis or by direct fusion with the plasma membrane. The latter pathway often leads to syncytia formation, caused by the fusion of infected cells with neighboring receptor-bearing cells. Yet, the implications of these two alternative entry routes for viral fitness and evolution remain poorly understood. To address this, we used a vesicular stomatitis virus-based system engineered to express the SARS-CoV-2 spike. Because deletion of the spike furin cleavage site (ΔFCS) abolishes plasma membrane fusion and restricts entry to the endocytic pathway, we compared Wuhan and ΔFCS spike variants. We found that plasma membrane entry allowed the Wuhan spike to accelerate infection and viral spread through syncytia formation. In contrast, the ΔFCS

SUBMITTER: Carrascosa-Saez M 

PROVIDER: S-EPMC12691665 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature