Examining the effects of environmental compounds on influenza virus ecology

Abstract

Influenza A virus (IAV) is a global threat. Infections in humans and highly-pathogenic IAV outbreaks in livestock substantially burden the economy. All past pandemics of IAV in humans and outbreaks in livestock have origins in viruses that previously circulated among wild aquatic birds, which are the natural reservoir for the virus. IAV can also jump from wild birds into other animals including marine mammals. This thesis explores the effects of environmental compounds, including bacteria and pollutants, on the ecology of IAV. In the first study, I demonstrate that gastrointestinal tract bacterial isolates reduce the thermal stability of IAV. Moreover, bacterial lipopolysaccharide (LPS), found on the exterior surfaces of bacteria, is sufficient to significantly decrease the stability of both human and avian viral strains at the physiological temperatures of their respective hosts. I also examine how subtype and host-origin of the viruses affect the extent to which IAV is susceptible to LPS and show that LPS binds directly to virions affecting their morphology. For my second project, I examine how environmental pollutants, specifically persistent organic pollutants (POPs) in the context of marine mammals, affect the replication of IAV using an in vitro approach. While it is known that POPs can suppress the immune response in animals to increase susceptibility to infectious disease, I found that POPs interact with both host-cells, by altering gene expression, and virions directly, by damaging viral envelopes. Taken together, these results demonstrate that environmental compounds have the ability to modulate IAV infectivity by interacting indirectly with host's immune system and also directly with the virions. The studies presented in this thesis provide insights into IAV ecology by highlighting the potential risks of antibiotic overuse in livestock and the exposure of humans to pollutants.