Heterogeneity across mammalian- and avian-origin A(H1N1) influenza viruses influences viral infectivity following incubation with host bacteria from the human respiratory tract

Influenza A viruses (IAV) are primarily transmitted between mammals by the respiratory route, and encounter bacteria in the respiratory tract before infecting susceptible epithelial cells. Previous studies have shown that mammalian-origin IAV can bind to the surface of different bacterial species and purified bacterial lipopolysaccharides (LPS), but despite the broad host range of IAV, few studies have included avian-origin IAV in these assessments. Since IAV that circulate in humans and birds are well-adapted to replication in the human respiratory and avian gastrointestinal tracts, respectively, we investigated the ability of multiple human and avian A(H1N1) IAV to associate with bacteria and their surface components isolated from both host niches. Binding interactions were assessed with microbial glycan microarrays, revealing that seasonal and avian IAV strains exhibited binding diversity to multiple bacterial glycans at the level of the virus and the bacterium, independent of sialic acid binding preference of the virus. Co-incubation of diverse IAV with LPS derived from Pseudomonas aeruginosa (P. aeruginosa), a respiratory tract bacterium, led to reduced retention of viral infectivity in a temperature dependent manner which was not observed when co-incubated with LPS from Escherichia coli, a gut bacterial isolate. Reduction of viral infectivity was supported by disruption of IAV virions following incubation with P. aeruginosa LPS using electron microscopy. Our findings highlight that both human and avian IAV can bind to bacterial surface components from different host sites resulting in differential functional interactions early after binding, suggesting the need to study IAV-bacteria interactions at the host range interface.