ena-STUDY-Institute for Biomedical Sciences - Georgia State University-26-08-2019-18:48:30:160-214
Impact of resident microbiota on viral infection is poorly defined. Investigation of mice spontaneously resistant to rotavirus reveals that high levels of segmented filamentous bacteria confer resistance to rotavirus independent of interferon or adaptive immunity.
Enteric viruses encounter epithelial cells amidst a diverse microbial ecosystem. Hence, we hypothesized that our unintentional generation of a rotavirus (RV)-resistant colony of Rag1-KO mice reflected microbiota composition influencing RV infection. Indeed, the RV-resistant phenotype was transferrable via both co-housing or fecal transplant. Incubation of RV with feces from RV-resistant, but not RV-susceptible, mice greatly attenuated RV infection of epithelial cells in vitro suggesting the RV-resistant phenotype resulted from direct microbiota-RV interactions. Interrogation of microbiotas that conferred RV-resistance via antimicrobial agents, heat treatment, and filtration, followed by limiting dilution transplant to germ-free mice and subsequent fecal DNA sequencing revealed a central role for segmented filamentous bacteria (SFB), which, was sufficient to protect against RV in vitro and in vivo. Such protection was independent of lymphocytes (innate and adaptive), IL-17, IL-22, and was not associated with any observable negative health consequences. Thus, irrespective of its ability to impact immune cells, SFB confers protection against enteric viral infection and associated diarrheal disease.
Enteric viruses encounter epithelial cells amidst a diverse microbial ecosystem. Hence, we hypothesized that our unintentional generation of a rotavirus (RV)-resistant colony of Rag1-KO mice reflected microbiota composition influencing RV infection. Indeed, the RV-resistant phenotype was transferrable via both co-housing or fecal transplant. Incubation of RV with feces from RV-resistant, but not RV-susceptible, mice greatly attenuated RV infection of epithelial cells in vitro suggesting the RV-resistant phenotype resulted from direct microbiota-RV interactions. Interrogation of microbiotas that conferred RV-resistance via antimicrobial agents, heat treatment, and filtration, followed by limiting dilution transplant to germ-free mice and subsequent fecal DNA sequencing revealed a central role for segmented filamentous bacteria (SFB), which, was sufficient to protect against RV in vitro and in vivo. Such protection was independent of lymphocytes (innate and adaptive), IL-17, IL-22, and was not associated with any observable negative health consequences. Thus, irrespective of its ability to impact immune cells, SFB confers protection against enteric viral infection and associated diarrheal disease.