Viral infections can have detrimental effects worldwide, leading to declining economies, loss of school days, workdays, numerous physician visits, hospitalizations, and death. Concerning respiratory viral infections, viruses belonging to the families Orthomyxoviridae (influenza virus) and Coronaviridae (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) have been prominent causes of morbidity and mortality worldwide, resulting in previous and current epidemics and pandemics. Multiple biological and environmental factors such as sex, age, nutrition, disease status, and the host residential microbiome can affect the pathogenesis and transmission of respiratory viruses.The studies presented here aimed to investigate environmental and host factors influencing respiratory virus pathogenesis and transmission in vitro and in vivo using two primary pathogens, influenza A virus (FLUAV) and SARS-CoV-2. I used molecular virology techniques and bioinformatic tools to analyze virus infection and transmission using in vitro systems. I also assessed pathogenesis and changes within the respiratory and intestinal tract in two animal models post-respiratory virus infection. I designed a model system to study FLUAV transmission in vitro. The results showed successful aerosol inoculation of three subtypes of FLUAV (H1N1, H3N2, and H9N2) in a common cell line, Madin-Darby canine kidney (MDCK) cells. Further, I was able to infect differentiated human airway epithelial cells with the H1N1 and H3N2 FLUAV utilized within these studies. Assessing aerosol inoculation in an in vitro system can be valuable in testing molecular markers associated with increased respiratory transmission. My advances a technique that can be utilized to assess molecular markers involved in FLUAV transmission prior to in vivo testing.
In addition to understanding aerosol transmission, I analyzed the effect of various biological and environmental factors on the pathogenesis of FLUAV and SARS-CoV-2 in vivo. First, I tested the effect of antibiotic growth promoter administration on FLUAV infection in broiler chickens, including the impact of virus shedding and dysbiosis of the respiratory and intestinal microbiome. In addition to analyzing environmental factors, I examined the effect of FLUAV exposure prior to SARS-CoV-2 infection on viral titers, disease pathology, and the respiratory and intestinal microbiome in aged Golden Syrian hamsters. Both studies showed changes within the respiratory and intestinal microbial community, notably the enrichment of opportunistic pathogens and microbes associated with inflammation. The relationship between the residential microbiome and other confounding factors such as respiratory virus infection, age, and antibiotic growth promoter administration contributes to a better understanding of the complexities associated with the host responses during viral infections.
