Seminar: Mariya Goncheva

Partners in pathogenesis: Understanding the interplay between influenza A virus and bacteria during respiratory infection

Influenza A virus (IAV) remains a major cause of respiratory disease worldwide. A significant complication of primary IAV infection is secondary bacterial infection, which can substantially increase disease severity and mortality. While considerable research has focused on how influenza predisposes the host to bacterial disease, much less is known about the reciprocal interaction and how bacteria influence viral replication. Our work demonstrates that Staphylococcus aureus can directly enhance IAV replication through manipulation of host cell biology. We identified the S. aureus surface protein fibronectin-binding protein A (FnbA) as a key bacterial factor driving this pro-viral phenotype. FnbA-dependent enhancement of IAV replication was conserved across multiple viral strains and was associated with reduced abundance of the host vesicular trafficking proteins VPS26A and VTA1. Rather than substantially altering viral protein production or localization, S. aureus increased the proportion of infectious progeny particles and promoted the release of infectious virions from infected cells. Together, these findings reveal an unexpected role for a well-characterized bacterial surface protein in modifying the replication of a co-infecting virus. This work highlights the reciprocal nature of viral-bacterial interactions and demonstrates that bacterial pathogens can actively reshape host cell processes to promote viral replication.