A innate immune sensor has been discovered that detects the presence of stomach viruses in the body. This protein, named MDA-5, triggers an immune response, and might give scientists information to develop a treatment to prevent or reduce infections of this kind, according to an article released on July 18, 2008 in the open access journal PLoS Pathogens.
Norovirus, commonly called the stomach flu but actually unrelated to influenza, is a common infection in areas where people live close together. These might include cruise ships, nursing homes, military bases and schools. Therapy methods are limited for this kind of infection, because it is a virus and thus unaffected by antibiotics. Recently, scientists have developed methods to grow noroviruses in the laboratory and study them in vitro.
The initial study concluded that the absence of MDA-5 in cells inhibits the immune response against norovirus. However, this is not the only protein involved in this process. “Our research strongly indicates that MDA-5 is the primary sensor for norovirus infection, but the body’s ability to detect the virus is so important that it doesn’t just rely on one sensor,” stated Marco Colonna, M.D., professor of pathology and immunology. “We found that another protein sensor [TLR3] serves as a back-up and there may be others that have not yet been discovered.”
To investigate the immune response more completely, scientists at the Washington University School of Medicine in St. Louis investigated two groups of mice: one incapable of synthesizing the protein MDA-5, and one unable to make the protein TLR3. Both groups were exposed to norovirus and the response was measured. Both groups of deficient mice had defective immune responses to the norovirus in their bodies, and the mice missing MDA-5 had higher levels of the virus in their bodies.
Both of these proteins are intracellular signals. MDA-5, and to some degree TLR3, induce other cells to produce interferon, a chemical that terminates virus production and begins the immune attack in the body. The researchers suspected that they might be important in norovirus recognition because they are already known to recognize similar infections. While this work was done in mice, there is a relatively high level of homology between mice and humans, so it is likely that similar proteins exist in humans. In fact, some people have common variations of the MDA-5 gene that could make them more sensitive to norovirus infection — for these people, a potential norovirus treatment would be especially useful.
MDA-5 Recognition of a Murine Norovirus.
McCartney SA, Thackray LB, Gitlin L, Gilfillan S, Virgin IV HW, et al.
PLoS Pathog 4(7):e1000108.
doi:10.1371/journal.ppat.1000108
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Written by Anna Sophia McKenney