Role of Commensal Bacteria in Promoting Environmental Persistence & Transmission of Influenza A Virus

Influenza virus is a respiratory pathogen of global importance with high economic and health-care burdens. This virus infects 10-20% of the population every year, causing an estimated one billion cases of disease, approximately 400,000 deaths, and an annual economic burden of billions of dollars. Though dwarfed by the COVID-19 pandemic over the last 2 years, influenza virus has continually circulated within the human population since the first recorded pandemic over a century ago. During this outbreak of 'Spanish Flu', influenza virus killed an estimated 50 million people, and recurrent clusters of human infection with avian influenza viruses (e.g. H5N1, H7N9) pose a real risk for a repeat pandemic scenario in coming years. The globalization of our world paired with ever-growing agricultural practices potentiates this risk for an influenza pandemic, which we remain under-equipped to deal with. Vaccines for influenza virus are available, however they fail to induce cross-reactive immunity and must be updated and re-administered every year to cover new variants. They are also insufficient to protect against emergent strains from zoonotic sources (e.g. avian influenza H5N1 and H7N9). As an alternative strategy to vaccines, health-care policies also aim to reduce the impacts of influenza by preventing virus transmission. However, an incomplete understanding of the complexity of transmission continues to hamper progress towards this goal. Upon exit from a host, influenza virus encounters an array of hostile conditions, including desiccation from an abrupt change in relative humidity, RH (from approximately 100% within the respiratory cavity down to 40-60% in most indoor environment) and a change in temperature. Unless the environment is incredibly humid, virus-containing aerosols will rapidly evaporate to approximately half their initial diameter, inadvertently increasing the concentrations of internal salts and other components by nearly an order of magnitude. This process also lowers the internal pH of the particle dramatically. Influenza virus is additionally affected by external factors of solar ultraviolet (UV) radiation, and other open air factors (e.g. ozone). Despite these stressors, infectious viruses are readily detected in exhaled aerosols from human patients. This indicates mechanisms of protection or virus persistence are at play. Respiratory matrices (e.g. mucin) are hypothesized to stabilize influenza virus against environmental inactivation, but this has not conclusively been shown and exact nature of this stabilization is only postulated. Furthermore, commensals of the respiratory niche pose another potential 'stabilizer' that have not comprehensively been examined. Binding interactions between enteric viruses and resident bacteria have been reported in the past, and are known to increase viral stability for a number of enteric viruses, especially against heat stress and other inactivating treatments. Despite substantial microbial diversity in the respiratory tract, there has been limited research into similar pathogen co-operations, particularly from the perspective of virus stability during airborne transmission. This project seeks to unravel the mechanisms of virus inactivation and persistence in this setting. Findings will improve our understanding of influenza spread and persistence outside the host, and knowledge gained may enable development of novel air treatments or therapeutics to limit virus persistence, collectively improving our capacity to control respiratory virus outbreaks in our future.