Specific coxsackievirus B3 binding interactions with bacteria

The National Institute of Allergy and Infectious Diseases, part of the Department of Health and Human Services, awarded the Trustees of Indiana University $129,915 on December 29, 2025, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct research characterizing the binding interaction between Coxsackievirus B3 (CVB3) and enteric bacteria.

CVB3 is an enteric virus that causes viral myocarditis and other serious infections. The research addresses a gap in understanding how CVB3 binds to intestinal bacteria such as Salmonella enterica and Escherichia coli. Prior studies have shown that CVB3 interacts with certain bacteria in ways that enhance viral stability, infectivity, replication, and pathogenesis, and that this enhancement is species-specific and depends on bacterial cell wall components. For example, smooth-type lipopolysaccharide from S. enterica enhances CVB3 stability, while rough-type LPS and E. coli LPS do not. However, the mechanism by which CVB3 binds to bacteria and whether binding trends affect bacteria-mediated viral enhancement remain unknown. This project will characterize the specific binding interactions between CVB3 and enteric bacteria to clarify which bacterial cell wall components are responsible for binding and viral enhancement.

The work is performed at Indiana University Indianapolis in Indianapolis, Indiana, with a period of performance extending from December 29, 2025, to July 31, 2027. This is a project grant, the standard assistance type for individual research awards under the NIAID program.

Abstract

Enteric viruses are infectious human pathogens that lead to significant disease and symptoms such as nausea, diarrhea, vomiting, and abdominal pain. These viruses spread through the fecal-oral route, initiating infection in the intestine and traverse through the gastrointestinal tract. Enteric viruses are easily spread by contamination of food and water and by contact between individuals. Coxsackievirus is a type of enteric virus that causes hand, foot, and mouth disease, aseptic meningitis, conjunctivitis, and myocarditis. Specifically, coxsackievirus B3 (CVB3) is the major isolate associated with viral myocarditis. Because CVB3 is an enteric virus and initiates infection in the gastrointestinal tract, the virus encounters a diverse population of intestinal bacteria. Previous studies have shown that CVB3 interacts with bacteria and that this interaction enhances viral stability, infectivity, replication, and pathogenesis. Our lab has also shown that bacteria-mediated enhancement is specific to bacterial species as well as to species-specific bacterial cell wall components. Notably, salmonella enterica was able to enhance CVB3 infectivity, but not escherichia coli. Furthermore, specific bacterial cell wall components are able to enhance CVB3 stability. Smooth type LPS from s. Enterica was able to enhance CVB3 stability, but not rough type LPS nor any LPS from e. Coli strains. Interestingly, CVB3 is able to bind to both s. Enterica and e. Coli despite these differences in bacteria-mediated viral enhancement. Previous data demonstrate that enteric viruses can bind directly to bacteria, including CVB3. However, IT is unknown if binding trends affect bacteria-mediated viral enhancement or if specific components of bacterial cell walls are responsible for binding. The overarching goal of this project is to characterize the binding interaction between CVB3 and enteric bacteria. Our central hypothesis is that CVB3 binds enteric bacteria through specific LPS structures that dictate binding affinity. To examine this hypothesis, i will perform biochemical binding assays to identify the specific bacterial cell wall structures that allow for bacterial binding to CVB3. I will also compare binding affinities between CVB3 and different intestinal bacteria. Experiments outlined in aim 1 will establish the role that LPS plays in binding to CVB3 and identify the specific components of LPS that are required for CVB3 binding. Experiments described in aim 2 will widen the scope of this study by examining differences in CVB3 binding trends to different intestinal bacteria and LPS structures from different bacterial species. Overall, these data will distinctly characterize the interactions between CVB3 and enteric bacteria. Completion of this project will reveal more about the mechanisms driving bacteria-mediated enhancement of CVB3 and will provide insight into potential conserved features between CVB3 and other enteric viruses. This will increase our understanding of the pathogenesis of enteric viruses and guide future therapeutic avenues.