Researchers isolated gut bacteria that can prevent and cure rotavirus infection

Rotavirus Infection and Gut Bacteria

Highlights

• Some mouse colonies developed spontaneous resistance to rotavirus (RV) infection
• Fecal microbial transplantation transfers RV resistance
• Protection against RV was mediated by segmented filamentous bacteria (SFB), Candidatus arthromitus
• SFB block RV by increasing epithelial cell turnover

Rotaviral Infections

Enteric viral infections remain a major public health challenge. Persons with immune dysfunction are susceptible to develop chronic infections by normally transiently infecting diarrheagenic viruses, such as RV and norovirus. Most humans are exposed to RV multiple times, there is substantial heterogeneity in disease penetrance and severity both geographically and within a given population. Some RV infections result in only mild disease, whereas others cause severe life-threatening diarrhea.

Rotaviral Machinary of Infection

This work is done by Andrew T. Gewirtz to check the role of microbes influencing RV infection published in Cell. RV typically requires adaptive immunity for clearance. Rotavirus (RV), a nonenveloped double-stranded RNA (dsRNA) virus, remains a major world-wide scourge, causing life-threatening diarrhea. RV enters its host orally and primarily infects ileal villous epithelial cells. Upon infection it encounters the gut microbiota. The gut microbiota protects against pathogenic bacteria. For example, antibiotic-treated hosts are highly prone to colonization and disease by bacterial pathogens. Removal of the microbiota in mice via germ-free (GF) or antibiotic method leads to infection with mouse mammary tumor virus, poliovirus, reovirus, and RV.

RV is typically cleared within 10 days, but immunodeficient humans and mice, including C57BL/6 Rag1-KO mice, develop chronic RV infection. They showed that transmissible agents present in GSU-RAG (RV-resistant Rag1-KO mice) feces protect against RV infection and its major associated disease. They also showed that GSU-RAG feces transiently protect immunocompetent mice from RV. Transplanting GSU-RAG feces into JAX-RAG (RV-susceptible Rag1-KO mice) mice did not increase IL-22 expression nor did such transfer result in elevations in IL-18 suggesting such RV resistance is not mediated by these components. They have ruled out the role of other immune function in the RV resistant by several other experiments. These results suggest that microbes in GSU-RAG feces may have broad antiviral activity. The GSU-RAG microbiota may directly interact with viruses to reduce infectivity.

The capacity of GSU-RAG feces to suppress viral infection in vitro was not specific for RV but also extended to VSV and influenza A virus (IAV). Next, they sought to define the protective component of GSU-RAG. There results suggest that GSU-RAG mice were protected from RV infection by heat-stable, possibly spore-forming, bacteria that are readily transmitted to immunodeficient mice from which it may be difficult to clear when established. Analysis of the microbiome in these transplanted mice revealed that a striking percentage (95%) of 16S sequences corresponded to a single species of bacteria, Candidatus arthromitus, more commonly referred to as SFB. Assay of SFB by qPCR indicated that SFB were uniformly present in feces of GSU-RAG but not JAX-RAG mice. These data suggesting that SFB might contribute to RV resistance. There results also suggest that SFB promotion of enterocyte proliferation, migration, and subsequent luminal shedding contributes to its protection against RV. There all results highlighting the potential utility of gut microbiota members to prevent and treat viral infections.

The Cure

This study suggesting a new mechanism by which the gut microbiota can improve health. An improved understanding of the mechanisms by which SFB promote RV resistance may ultimately lead to new approaches to prevent and treat viral infections. Investigation of the effect of SFB on the host may reveal previously unappreciated innate antiviral signaling pathways, whereas the microbiota itself might be a possible source of antiviral agents. Marine microbial ecosystem for antiviral compounds yielded cyanovirin-N, a protein produced by a Cyanobacteria strain isolated from algae that displays direct antiviral activity against HIV. They speculated that other microbiota products yet to be discovered diminish viral infection and could be harnessed to develop new, potentially broad-spectrum antiviral strategies.

Journal Reference

1. 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. Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection. Cell, 2019 DOI: 10.1016/j.cell.2019.09.028