IFIH1/MDA5 in the innate immune response to coxsackievirus infection

Genome-wide association studies identified recently a type 1 diabetes locus in the gene melanoma differentiation-associated protein-5 (mda5, also denoted ifih1), coding for the viral RNA sensor MDA5. Variants of mda5 modify the risk for disease development [Smyth et al., 2006; Nejentsev et al., 2009]. Enteroviruses, such as Coxsackie B viruses (CVB), have been implicated in the aetiology of type 1 diabetes. A recent study was undertaken to determine whether MDA5 is important in the host response to CVB infection [Hühn et al., 2010]. C57BL/6 and 129/SvJ mice lacking mda5 were infected with CVB serotype 3 (CVB3). Mice deficient in MDA5 showed a dramatically increased susceptibility to CVB3 infection. The loss of MDA5 allowed the virus to replicate more rapidly, resulting in increased damage of the pancreas and the liver. The pancreatic islet cells were spared from damage, and none of the infected animals developed diabetes or hyperglycemia. It was also found that MDA5 is not absolutely necessary for the induction of type 1 interferons (IFNs), but is required for the production of maximal levels of systemic IFN-α early after infection. In conclusion, MDA5 plays an important role in the host immune response to CVB3. By restricting virus replication it protects the host from tissue damage and inflammation. These results encourage further studies on the possible role of mda5 in regulating susceptibility to virus-induced diabetes. J. Med. Virol. 83:1674–1674, 2011. © 2011 Wiley-Liss, Inc.