Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection

Zhenda Shi, Jun Zou, Zhan Zhang, Xu Zhao, Juan Noriega, Benyue Zhang, Chunyu Zhao, Harshad Ingle, Kyle Bittinger, Lisa M. Mattei, Andrea J. Pruijssers, Richard K. Plemper, Timothy J. Nice, Megan T. Baldridge, Terence S. Dermody, Benoit Chassaing, Andrew T. Gewirtz

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. Although RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immunodeficient mice, which, we hypothesized, reflected select microbes protecting against RV. Accordingly, such RV resistance was transferred by co-housing and fecal transplant. RV-protecting microbiota were interrogated by heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germ-free mice and microbiome analysis. This approach revealed that segmented filamentous bacteria (SFB) were sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of previously defined RV-impeding factors, including interferon, IL-17, and IL-22. Colonization of the ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. Incubation of RV with SFB-containing feces reduced infectivity in vitro, suggesting direct neutralization of RV. Thus, independent of immune cells, SFB confer protection against certain enteric viral infections and associated diarrheal disease.

Original languageEnglish
Pages (from-to)644-658.e13
JournalCell
Volume179
Issue number3
DOIs
StatePublished - Oct 17 2019

Keywords

  • fecal transplant
  • germ-free mice
  • infectious diarrhea
  • microbiota-virus interactions
  • rotavirus
  • segmented filamentous bacteria
  • viral gastroenteritis

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    Shi, Z., Zou, J., Zhang, Z., Zhao, X., Noriega, J., Zhang, B., Zhao, C., Ingle, H., Bittinger, K., Mattei, L. M., Pruijssers, A. J., Plemper, R. K., Nice, T. J., Baldridge, M. T., Dermody, T. S., Chassaing, B., & Gewirtz, A. T. (2019). Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection. Cell, 179(3), 644-658.e13. https://doi.org/10.1016/j.cell.2019.09.028