Norovirus is a highly contagious virus that affects the gastrointestinal tract and is best known for spreading rapidly on cruise ships, in nursing homes, schools and other densely populated spaces. Its host cell type has remained unknown, as well as much of its underlying mechanisms that drive infection. New findings published in Science now reveal that the norovirus cell type of choice are the rare tuft cells that function as immune sensors. The work comes from a team led by Washington University researchers.
"We were most surprised that the virus infects such a rare cell type and that even with so few cells infected, the infections can be intense and easily transmitted. In a single mouse, for example, maybe 100 cells will be infected, which is very few compared with other viruses such as the flu," said study first author Craig B. Wilen.
Tuft cells are intestinal epithelial cells that trigger an immune response upon detection of parasitic infections. Through experiments in mice, the team found that tuft cells carrying a particular receptor, CD300lf, were the virus’s specific target. They also found that type 2 cytokines, which are involved in protection against parasites, induced proliferation of the tuft cells. As a result, norovirus infection was amplified. This type of immune signaling may help explain why there is a greater risk of death from norovirus in areas of the world where worm infections are common.
The team also noted that noroviruses tucked inside tuft cells are effectively hidden from the immune system. This could explain why certain people, dubbed “healthy carriers,” continue to shed the virus long after the symptoms of illness disappear.
"This raises important questions about whether human norovirus infects tuft cells and whether people who have chronic norovirus infections and continue to shed the virus long after infection do so because the virus remains hidden in tuft cells," Wilen said. "If that's the case, targeting tuft cells may be an important strategy to eradicate the virus."
Image: An X-ray crystallographic structure of the Norovirus virus capsid. Image courtesy of Prasad, B.V et. al and RCSB PDB.