Scientists identify intestinal target cell of norovirus


View:136 Time:2018-04-13


A study, carried out by researchers from Washington University School of Medicine, the University of Illinois at Chicago College of Medicine, Harvard T. H. Chan School of Public Health, New York University School of Medicine, and Genentech, has identified that tuft cells carrying the CD300lf receptor are the specific target of norovirus, one of the most common stomach bugs worldwide. 

Outbreaks of the winter vomiting bug -- norovirus -- occur now and then. For instance, the 2018 Winter Olympics was plagued by the virus. Norovirus infections cause gastroenteritis, which is generally mild and of short duration. Common symptoms include sudden onset of vomiting (more common in children) and diarrhea (more common in adults), nausea, abdominal pain or cramps, malaise, low-grade fever, and muscle pain. These symptoms generally go away within several days, and the majority of people recover completely without treatment. But for infants, the elderly, and patients with certain diseases, norovirus symptoms can be serious and need medical care. Each year, norovirus kills about 200,000 people, particularly in low-income countries.

Unfortunately, no specific treatment or vaccine is available for such a common and potentially life-threatening virus. This is largely due to the lack of comprehensive understanding of how norovirus infection gets started. Moreover, it's somewhat difficult to grow human norovirus in the lab. People may continue to shed virus in their feces for up to two weeks after recovery. This is also a reason why norovirus outbreaks happen now and then. To develop effective treatments and vaccines to prevent norovirus outbreaks, it's essential to get a deeper understanding of how the virus infects humans.

The researchers investigated murine norovirus. In the previous study, the researchers identified the CD300lf protein as a murine norovirus (MNoV) receptor. For the current study, they discovered that tuft cells, a rare type of intestinal epithelial cell, express CD300lf and are the target cell for MNoV in the mouse intestine. In addition, they found that the type 2 cytokines, IL4 and IL-25, induce tuft cell proliferation and promote MNoV infection in vivo. Furthermore, infected tuft cells are resistant to immune clearance.

Tuft cells, or called brush cells, are chemosensory cells found in the intestines and respiratory tract. Tuft cells make up a small fraction of intestinal epithelial cells but expand quickly when parasites colonize or infect the gut. Studies have suggested that tuft cells are a key player in immunity to parasites. Given that intestinal parasite infections cause tuft cells to increase and norovirus infects tuft cells, it is not difficult to understand that intestinal parasite infections may cause norovirus to replicate more efficiently and result in more severe norovirus infection. This may be the reason why norovirus deaths are mainly found in low-income countries, where parasite infections are more common.

In conclusion, the new study reveals that noroviruses infect tuft cells and therefore evade the attacks by the host's immune system. This discovery offers an explanation for why people continue to shed noroviruses after recovery. Furthermore, targeting tuft cells could be a way to combat norovirus.

The full paper "Tropism for tuft cells determines immune promotion of norovirus pathogenesis" can be read in the 13 Apr 2018 tissue of the journal Science.
 
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