Female obese mice have a higher mortality rate and altered immune responses following viral infection in comparison to wild type mice

Abstract A rise in adiposity in the United States has resulted in >70% of adults being overweight or obese. Globally, areas that have seen a rise in obesity also have an increase in viral pathogens, resulting in a double disease burden. Studies done using influenza, hepatitis C, West Nile and dengue viruses have shown that excessive adiposity alters immune responses to vaccination. Similarly, obese individuals have a greater risk for developing COVID-19 following SARS-CoV-2 infection and a higher mortality rate than non-obese individuals. However, limited studies have been done to identify mechanisms responsible for obesity-induced impaired immune function. Based on published studies and our preliminary data, we hypothesized that obesity-associated chronic inflammation alters the immune system, enhancing susceptibility to viral diseases and hindering vaccine efficacy. To study this, we are using West Nile virus and SARS-CoV-2 in murine models of obesity. By infecting regular chow-fed (wt) and high fat diet-induced obese (ob) mice, we compared virus-specific immune responses at varying time points post infection. Results from these studies indicate that female ob mice have a higher mortality rate, dysfunctional virus-specific T cell responses and lowered efficacy of neutralizing antibodies. However, ob males do not show these differences when compared to wt males. These results demonstrate that obesity can enhance disease severity following viral infection which may have long term consequences for the generation of protective immune responses to vaccination, and sex appears to play a role in this phenomenon. Our ongoing studies are focused on determining how sex and chronic inflammation alter immune responses to these viral pathogens.