Subtype and host-origin of the viruses were shown to affect the extent to which IAV was susceptible to LPS. Furthermore, using a receptor-binding assay and transmission electron microscopy, we observed that LPS binds to and affects the morphology of influenza virions.Influenza A virus (IAV) is a global threat, infecting 5-10% of adults and 20-30% of children globally every year
5, and infections in humans and highly-pathogenic IAV outbreaks in livestock substantially burden the economy 6,7 . .Commensal bacteria and their products can indirectly protect against IAV infection by interacting with the host's immune system (Fig. 1A). In the absence of commensal bacteria, mice produced impaired type I/II interferon responses, CD4/CD8 T cell responses, and antibody production to All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/146266 doi: bioRxiv preprint first posted online Jun. 5, 2017; 3 IAV infection 3,4 . Moreover, mice pretreated with bacterial lipopolysaccharide (LPS), a product present on the exterior surface and shed by all Gram-negative bacteria, triggered a TLR4 mediated antiviral response to protect the hosts from lethal infection with IAV 12,13 . In contrast, LPS binds directly to the capsid protein of poliovirus, increasing cell attachment and the ability of the virions to remain infectious at increased temperatures 14 , and LPS binding to mouse mammary tumor virus (MMTV) enables increased immune evasion and successful transmission of the virus 15,16 . In the case of influenza, it is unclear whether commensal bacteria and LPS are interacting directly with IAV in addition to their indirect effects on the immune system.We first tested whether GI tract-derived bacteria can affect the stability of IAV. A panel of thirteen heat-killed bacteria derived from the GI microbiome (Table S1), standardized by protein content, and a water control were incubated individually with a human WSN H1N1-GFP virus for 1h at 48 °C. Stability was assessed by measuring the percentage of infected cells (those expressing GFP) by flow cytometry after an overnight infection. Eleven of the thirteen bacterial strains significantly decreased the stability of the virus after incubation compared to the water control (Fig. 1B). Our results indicate the reduction in infectivity was not due to the diluted bacterial products being cytotoxic ( Fig. S1A), nor was the decrease in infectivity due to the presence of bacteria or their products limiting the susceptibility of host-cells to infection (Fig. S1B). This suggests that the observed reduction in thermal stability may be due to the virus interacting directly with the bacterial cells and/or their products.Because there was a wide range in the extent to which bacterial strains reduced viral stability, the specific composition of a host's microbiome could influence its susceptibility to infectio...