Tuft cells are the targets of norovirus infection in mice, according to a new study published in Science. The findings have important implications for understanding norovirus pathogenesis and how interactions with other gut organisms alter the disease.
Globally, human noroviruses are the leading cause of acute viral gastroenteritis, an important disease burden responsible for around 200,000 deaths a year. There are no vaccines or antiviral therapies for human noroviruses, in part because understanding of the mechanisms of norovirus pathogenesis is limited.
In a new study, Craig Wilen and colleagues sought to shed light on how mouse noroviruses interact with the host and cause disease. “We use mouse norovirus as a model for human norovirus because mouse norovirus can replicate in cell culture and has a reverse genetics system,” says Wilen.
As the cellular tropism of norovirus in mice or humans was unclear, the researchers first used bone marrow transplants in a mouse model of norovirus infection to show that the target cell was radiation-resistant, and therefore an epithelial cell.
Immunofluorescence microscopy of the gut epithelium in these mice then revealed that tuft cells were the exclusive target of infection, a finding confirmed by flow cytometry. “Tuft cells are a very rare chemosensory cell in the lining of the gut that sense intestinal worms and parasites and then initiate an immune response,” explains Wilen. “It was quite surprising how so few infected cells (~100) per mouse could cause such substantial infection.”
Interestingly, tuft cell tropism might link helminth infection and the gut microbiota, which increase tuft cell numbers in the ileum and colon, respectively, to more severe norovirus infection in humans. “This finding may explain why there is greater human norovirus disease in regions that also have higher worm and parasite burdens,” Wilen remarks. Future research will aim to clarify how these findings translate to human norovirus infection.
Wilen, C. B. et al. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science 360, 204–208 (2018)
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Thomas, H. Tuft cells revealed as norovirus target. Nat Rev Gastroenterol Hepatol 15, 390 (2018). https://doi.org/10.1038/s41575-018-0027-4