Bacteria and bacterial envelope components enhance mammalian reovirus thermostability

Abstract

Enteric viruses encounter diverse environments as they migrate through the gastrointestinal tract to infect their hosts. The interaction of eukaryotic viruses with members of the host microbiota can greatly impact various aspects of virus biology, including the efficiency with which viruses can infect their hosts. Mammalian orthoreovirus, a human enteric virus that infects most humans during childhood, is negatively affected by antibiotic treatment prior to infection. However, it is not known how components of the host microbiota affect reovirus infectivity. In this study, we show that reovirus virions directly interact with Gram positive and Gram negative bacteria. Reovirus interaction with bacterial cells conveys enhanced virion thermostability that translates into enhanced attachment and infection of cells following an environmental insult. Enhanced virion thermostability was also conveyed by bacterial envelope components lipopolysaccharide (LPS) and peptidoglycan (PG). Lipoteichoic acid and N-acetylglucosamine-containing polysaccharides enhanced virion stability in a serotype-dependent manner. LPS and PG also enhanced the thermostability of an intermediate reovirus particle (ISVP) that is associated with primary infection in the gut. Although LPS and PG alter reovirus thermostability, these bacterial envelope components did not affect reovirus utilization of its proteinaceous cellular receptor junctional adhesion molecule-A or cell entry kinetics. LPS and PG also did not affect the overall number of reovirus capsid proteins σ1 and σ3, suggesting their effect on virion thermostability is not mediated through altering the overall number of major capsid proteins on the virus. Incubation of reovirus with LPS and PG did not significantly affect the neutralizing efficiency of reovirus-specific antibodies. These data suggest that bacteria enhance reovirus infection of the intestinal tract by enhancing the thermal stability of the reovirus particle at a variety of temperatures through interactions between the viral particle and bacterial envelope components.

Author summary

Enteric viruses are exposed to diverse environments during their replication cycle. They must be stable enough to endure outside their host, persist through changing pH and proteolytic environments encountered through passage via digestive and gastrointestinal tracts, and pliable to undergo disassembly during infection of host cells. Some enteric viruses have evolved to interact with and use members of the host microbiota to achieve optimal virion stability to infect their host. In this study, we show that the enteric mammalian reovirus (reovirus) interacts with bacteria. The interaction of the virus with bacteria or bacterial envelope components results in enhanced virion stability, which translates into enhanced reovirus infectivity following an environmental stress. The interaction of reovirus with bacterial envelope components does not alter receptor utilization, overall infection kinetics, or affect the anti-viral effects of reovirus-specific antibodies. Together, we show that reovirus has evolved to use Gram positive and Gram negative bacteria to provide enhanced virion stability at a variety of temperatures.