Enteric viruses encounter a vast microbial community in the mammalian digestive tract. However, the effect of the intestinal microbiota on enteric viruses is not well understood. Using mouse models, it was recently shown that intestinal bacteria promote infection with three unrelated enteric viruses, poliovirus, reovirus, and mouse mammary tumor virus. The enhanced replication and pathogenesis of these viruses in microbe-containing mice could occur through microbe-dependent effects on the host and/or virus. For the model picornavirus poliovirus, data suggest that bacterial products directly interact with virus particles and increase viral infectivity. Specifically, bacterial surface polysaccharides, such as lipopolysaccharide and peptidoglycan, enhance poliovirus infectivity by enhancing virion stability and aiding attachment to host cells. However, the precise mechanism of polysaccharide-mediated viral infectivity enhancement remains unknown. Similarly, virion and polysaccharide properties required for interaction and subsequent infectivity enhancement are unclear. By understanding specific mechanisms of microbiota-mediated virion infectivity enhancement, novel antiviral approaches are possible. The goal of this work is to define the virion and polysaccharide requirements for interaction and infectivity enhancement, and to examine mechanisms by which bacteria and bacterial surface polysaccharides enhance viral infectivity using poliovirus and Theiler's murine encephalitis virus as tractable picornavirus models. This will be accomplished through four specific aims: 1. Identify poliovirus virion properties required for microbiota/polysaccharide effects, 2. Define polysaccharide properties required for interaction with poliovirus, 3. Examine the mechanism by which polysaccharides enhance poliovirus infectivity, and 4. Examine microbiota effects on another picornavirus, Theiler's murine encephalitis virus (TMEV). It is likely that multiple enteric viruses benefit from the intestinal microbiota. Overall, enteric viruses may have evolved mechanisms to use gut microbes as an environmental sensor to initiate replication at the optimal site in the intestine. Understanding why enteric viruses require intestinal bacteria may inform antiviral and vaccine strategies to limit enteric virus infections.
Viruses that infect the intestinal tract are a major health problem, and how they interact with the gut environment is poorly understood. This work will examine how intestinal bacteria aid enteric viruses. By understanding bacteria-virus interactions in the intestine, new therapeutic and vaccine approaches are possible.
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