Researchers studying norovirus immune evasion have discovered that the virus may evade T cell detection by hiding out in rare immunoprivileged enteric cells. Their study was published this week in the journal Immunity.
Noroviruses cause 267 million infections and 20,000 deaths each year. While the virus generally clears within a few days, some suffer from persistent outbreaks that fail to clear for weeks or months. Furthermore, attempts to create a vaccine for the virus have so far been stymied by its apparent ability to escape immune detection in some.
Seeking to understand why this might be, a group of researchers from the Perelman School of Medicine tracked T cell responses in mice infected with either an acute or chronic strain of mouse norovirus. They were surprised to find that in both scenarios T cell function remained intact, eliminating T cell exhaustion as an explanation for the virus’s persistence.
Analyzing the T cell response, the team found two phases. In the first few days after infection, T cells react strongly and can control the virus, but after three days, they were no longer able to detect norovirus in 50 to 70% of mice infected with the chronic strain. In these mice, norovirus continued to be shed in their feces, indicating an active infection, but their T cells appeared to be “blind” to it.
The team conducted a series of experiments that tested the ability of T cells to respond to norovirus in different scenarios. In one, the T cells were co-cultured with infected gut cells, but no response was elicited until the cells were lysed to release their antigen.
The researchers found evidence that norovirus hides from immune cells in immunoprivileged gut cells. Experiments done by coauthors at Washington University indicated that norovirus may hide out in specialized, rare cells of the gut lining. The team is now working to further understand this aspect of norovirus infection.
Eventually, the team hopes this knowledge may help in the search for a norovirus vaccine and improve current therapies to treat the illness.
Image: Noroviruses can escape the immune system and still spread by hiding out in an extremely rare type of cell in the gut. Image courtesy of the Center for Disease Control and Prevention.