@article{5f3b9e88cb7e46d091ea93a9751411a7,
title = "Melanoma differentiation-associated protein-5 (MDA-5) limits early viral replication but is not essential for the induction of type 1 interferons after Coxsackievirus infection",
abstract = "Coxsackievirus infections are associated with severe diseases such as myocarditis, meningitis and pancreatitis. To study the contribution of the intracellular viral sensor melanoma differentiation-associated protein-5 (MDA-5) in the host immune response to Coxsackievirus B3 (CVB3) we infected C57BL/6 and 129/SvJ mice lacking mda-5. Mice deficient in MDA-5 showed a dramatically increased susceptibility to CVB3 infection. The loss of MDA-5 allowed the virus to replicate faster, resulting in increased liver and pancreas damage and heightened mortality. MDA-5 was not absolutely required for the induction of type 1 interferons (IFNs), but essential for the production of maximal levels of systemic IFN-α early after infection. Taken together, our findings indicate that MDA-5 plays an important role in the host immune response to CVB3 by preventing early virus replication and limiting tissue pathology.",
keywords = "Coxsackievirus, Diabetes, Enterovirus, Hepatitis, Innate immunity, Interferon, Melanoma differentiation-associated gene-5, Pancreatitis",
author = "H{\"u}hn, {Michael H.} and McCartney, {Stephen A.} and Katharina Lind and Emma Svedin and Marco Colonna and Malin Flodstr{\"o}m-Tullberg",
note = "Funding Information: Dr. J. Bergelson (University of Pennsylvania School of Medicine, Philadelphia, PA, USA) and colleagues are gratefully acknowledged for assistance with the RT-PCR analyses. These studies were supported by the European Foundation for the Study of Diabetes (EFSD) (M.F-T), the Erik and Edith Fernstr{\"o}ms stiftelse (M.H.H.), the Swedish Foundation for Strategic Research (M.F-T), the Swedish Research Council (M.F-T), The Swedish Diabetes Association Research Foundation (M.F-T). M.H.H, was also supported by an Albert Renold Fellowship from the EFSD. MC was supported by JDRF grant # 24-2007-420 . SM is supported by NRSA Award Number F30HL096354 from the NHLBI . The opinions in this manuscript as those of the authors and do not reflect the positions of the JDRF or NHLBI. ",
year = "2010",
month = may,
doi = "10.1016/j.virol.2010.02.010",
language = "English",
volume = "401",
pages = "42--48",
journal = "Virology",
issn = "0042-6822",
number = "1",
}