Researchers have long sought to identify the cells in the gut that are susceptible to infection by norovirus, the leading cause of viral gastroenteritis worldwide - and now one team has pinpointed the type of cell that falls victim. The finding could eventually lead to a therapy for this troublesome virus that infects 700 million people annually, causing symptoms such as diarrhea, vomiting, abdominal pain and in some cases death. In previous work, Craig B. Wilen and colleagues discovered that noroviruses use the receptor CD300lf to infect cells. However, this receptor is mostly thought to be expressed in blood stem cells, not cells lining the gut, where noroviruses take hold. Here, the team fluorescently marked CD300lf-expressing cells throughout the ilea and colons of mice, homing in a small subset called tuft cells, a rare chemosensory epithelial cell type found in both mice and humans. In analyzing millions of cells, the researchers found that norovirus infects tuft cells, but not regular epithelial cells in the gut. Reproduction of tuft cells is known to be boosted in the presence of two immune signaling proteins, IL-4 and IL-25, prompting Wilen et al. to assess whether these proteins facilitate the transmission of noroviruses in mice. Indeed, they found that administering both IL-4 and IL-25 significantly increased both the proportion of mice infected with virus and the abundance of viral particles within feces.
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Journal
Science