DESCRIPTION (provided by applicant): 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 shown that intestinal bacteria promote infection with four unrelated enteric viruses: poliovirus, reovirus, murine norovirus, and mouse mammary tumor virus. All of these viruses bind bacteria and/or bacterial surface polysaccharides, raising the possibility that bacteria may deliver virions to host cells to initiat the first viral replication cycle in the gut. Each bacterium binds multiple poliovirus or reovirus particles. Since bacteria are small compared to mammalian intestinal cells, a bacterium may deliver more than one virion per host cell. Bacteria-mediated delivery of multiple virions into an intestinal cell is interesting considering that a limited number of virions are transmitted and therefore the first replication cycle is likely initiated at an extremely low multiplicity of infecion (MOI). Bacteria may facilitate viral co-infection even when very few virions are present. Indeed, after exposure to bacteria in vitro or in vivo, genetically marked polioviruses generated chimeric plaques derived from multiple founders due to bacteria-mediated co-infection. These results raise questions about our concepts of MOI and plaque-forming unit (PFU)-what is an infectious unit? Since bacteria-bound viruses may initiate synchronous co-infection, do bacteria promote poliovirus genetic recombination or reassortment of reovirus genome segments? Many RNA viruses within a population have reduced fitness due to mutation and particle:PFU ratios are high: Does bacteria-mediated viral co-infection enhance viral replication and evolution? In this work, we will use poliovirus and reovirus as genetically tractable model viruses to test the hypothesis that bacteria mediate synchronous co-infection and therefore promote viral recombination or reassortment even when very few virions are present. This work has the potential to redefine how we think about "the viral infectious unit", which is relevant for all of virology.

PUBLIC HEALTH RELEVANCE: Viruses that infect the intestinal tract are a major health problem, but how they interact with the gut environment is poorly understood. This work will test the hypothesis that bacteria-bound viral particles initiate co-infection of host cells, thus promoting viral infection and viral evolution. By understanding how bacteria influence enteric virus infection, novel approaches to limit enteric virus transmission may be possible.