Research

Enteroviruses are some of the most common viruses infecting humans worldwide. It is estimated that these viruses cause an economic burden of seven billion dollars annually in the United States. Among enteroviruses, Coxsackievirus B3 (CVB3) is a primary cause of viral myocarditis, and approximately 5% of symptomatic infections are fatal. In spite of these burdens, there are no vaccines or treatments available for Coxsackievirus infections. Thus, there is a critical need to identify underlying mechanisms that dictate a protective immune response to CVB3. Our long-term goal is to elucidate factors that influence replication of Coxsackievirus and other enteroviruses to develop novel therapeutics and guide vaccine strategies.

Sex-bias in viral infections

Sex is a significant contributor to human disease. Males are often more susceptible to pathogens, while females are more predisposed to autoimmune diseases. Using an oral inoculation model to study CVB3, we found that male mice supported robust intestinal CVB3 replication and succumbed to CVB3-induced disease, whereas female mice did not. These results mirror the sex-bias in CVB3 disease in humans. Additionally, oral inoculation of gonadectomized mice reduced shedding and pathogenesis, suggesting a role for sex hormones during infection. Our current work suggests that testosterone is a key sex hormone in CVB3 pathogenesis following oral inoculation.

Virus-bacterial interactions

Intestinal bacteria enhance enteric virus pathogenesis. We have found that host intestinal bacteria influence CVB3 replication and pathogenesis. Recently, we determined that specific bacteria and bacterial cell wall components are required to enhance infectivity and stability of CVB3. Interestingly, the intestinal bacteria required to enhance CVB3 differed from poliovirus, a closely related enteric virus, suggesting that even related viruses may differ in their reliance on host microbiota. Overall, these data indicate that specific bacteria and their cell wall components dictate the interaction with various enteric viruses in distinct mechanisms.

SARS-CoV-2 Therapeutics

With the 2020 pandemic there is a need to develop novel therapeutics to combat SARS-CoV-2. To help in these efforts, we helped establish a BSL-3 laboratory on the Indiana University School of Medicine campus to help develop new treatments. In collaboration with multiple PIs on campus, we have screened and identified multiple compounds that impact SARS-CoV-2 infection.