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-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.
authors.affiliation: Center for Infectious Medicine F59, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hühn
authors.forename: Stephen A
authors.initials: SA
authors.lastname: McCartney
authors.forename: Katharina
authors.initials: K
authors.lastname: Lind
authors.forename: Emma
authors.initials: E
authors.lastname: Svedin
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Malin
authors.initials: M
authors.lastname: Flodström-Tullberg
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000201:enzymology / Q000276:immunology* / Q000821:virology*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology*; D004770:Enterovirus / Q000502:physiology*; D007370:Interferon Type I / Q000096:biosynthesis; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053585:Virus Attachment; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1