Journal
VIROLOGY
Volume 401, Issue 1, Pages 42-48Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2010.02.010
Keywords
Coxsackievirus; Enterovirus; Diabetes; Innate immunity; Interferon; Hepatitis; Melanoma differentiation-associated gene-5; Pancreatitis
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Funding
- European Foundation for the Study of Diabetes (EFSD)
- Erik and Edith Fernstroms stiftelse
- Swedish Foundation for Strategic Research
- Swedish Research Council
- Swedish Diabetes Association Research Foundation
- EFSD
- JDRF [24-2007-420]
- NHLBI [F30HL096354]
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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-alpha 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. (C) 2010 Elsevier Inc. All rights reserved.
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