ena-STUDY-Georgia State University-24-08-2019-01:17:14:551-160
Segmented filamentous bacteria prevent and cure rotavirus infection
Enteric viruses encounter epithelial cells amidst diverse microbiota. We hypothesized that our unintentional generation of rotavirus (RV)-resistant Rag1-KO mice reflected microbiota composition influencing RV infection. Accordingly, such RV-resistance was transferred by co-housing and fecal transplant. Interrogation of RV-protecting microbiotas via heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germfree mice and subsequent fecal DNA sequencing revealed a central role for segmented filamentous bacteria (SFB), which were sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of lymphocytes (innate and adaptive), interferon, IL-17, and IL-22. Colonization of ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover, which likely contributed to reducing RV burden. Yet, incubation of RV with SFB-containing feces reduced its infectivity in vitro, suggesting possible direct neutralization of RV. Thus, independent of immune cells, SFB confers protection against certain enteric viral infections and associated diarrheal disease.
Enteric viruses encounter epithelial cells amidst diverse microbiota. We hypothesized that our unintentional generation of rotavirus (RV)-resistant Rag1-KO mice reflected microbiota composition influencing RV infection. Accordingly, such RV-resistance was transferred by co-housing and fecal transplant. Interrogation of RV-protecting microbiotas via heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germfree mice and subsequent fecal DNA sequencing revealed a central role for segmented filamentous bacteria (SFB), which were sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of lymphocytes (innate and adaptive), interferon, IL-17, and IL-22. Colonization of ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover, which likely contributed to reducing RV burden. Yet, incubation of RV with SFB-containing feces reduced its infectivity in vitro, suggesting possible direct neutralization of RV. Thus, independent of immune cells, SFB confers protection against certain enteric viral infections and associated diarrheal disease.