Coxsackievirus B3 (CVB3) is a common infection that is spread by the fecal-oral route. Nearly all humans are infected with a coxsackievirus by the age of 5, and coxsackievirus is a major cause viral myocarditis, meningoencephalitis, and hand, foot, and mouth disease. Using a recently developed mouse model to study CVB3, I found that, similar to humans, male mice succumb to CVB3-induced disease, whereas female mice do not. Intriguingly, CVB3 replication in the intestine of male mice is enhanced and requires intestinal bacteria. Furthermore, CVB3 replication can be restored in female mice when they are given microbiota from male mice by fecal transplantation. This suggests, for the first time, that sex differences in intestinal bacteria alter viral replication. However, the mechanisms for this sex-bias remain unknown. Emerging data indicate that intestinal bacteria differ in males and females and that bacterial differences correlate with sex hormones, such as testosterone. These data suggest that bacteria and sex hormones may influence CVB3 replication in the intestine. The goal of this study is to identify intestinal bacteria that promote CVB3 replication and investigate the effect of sex hormones on intestinal CVB3 replication. These studies will shed significant insights into the intestinal environment required for coxsackievirus replication and will be beneficial to understanding human infections.

Public Health Relevance

Coxsackievirus is a major human pathogen and can cause disease in the heart, brain, and liver. These viruses initiate infection in the diverse environment of the gastrointestinal tract, yet the effect of this environment on intestinal infection is unclear. The goal of this proposal is to investigate the role of two environmental factors, sex hormones and intestinal bacteria, on coxsackievirus replication to shed light on human infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01DK110216-01
Application #
9163498
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Saslowsky, David E
Project Start
2016-09-01
Project End
2021-07-31
Budget Start
2016-09-01
Budget End
2017-07-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Robinson, Christopher M; Wang, Yao; Pfeiffer, Julie K (2017) Sex-Dependent Intestinal Replication of an Enteric Virus. J Virol 91: