Unique Aspects of Intestinal Biology That Influence Enteric Virus Infection

Enteric viruses are human pathogens that pose a significant global health problem. In this work, I explore how unique facets of host biology influence enteric virus infection, ranging from intestinal microbiota to circadian rhythms. To examine these factors, I used coxsackievirus B3 (CVB3) and poliovirus, which serve as a powerful model viruses to understand virus-host interactions. CVB3 and poliovirus are nonenveloped single-stranded positive-sense RNA viruses, which spread through the fecal-oral route. While many enteric virus infections are mild, some can be severe or even fatal. Thus it is important to study which factors impact enteric virus infection. Throughout my dissertation I used a variety of mouse models to answer a multitude of questions related to what factors influence enteric virus infection. To study the microbiota-mediated enhancement of CVB3 infection, I used different methods of antibiotic depletion in mice. We determined that two related enteric viruses, CVB3 and poliovirus, differ in their requirements of the microbiota. Furthermore, I studied the antiviral effects of antibiotics in vitro and in vivo and found that while antibiotics are not antiviral for CVB3 in cell culture, they are antiviral for CVB3 in a mouse model. Finally, by infecting mice at different times of day, we determined that host circadian rhythms influence enteric virus susceptibility. In conclusion, using model enteric viruses, such as CVB3 and poliovirus, I elucidated multiple unique aspects of host biology, ranging from microbiota to circadian rhythms, that influence viral replication and pathogenesis.