MDA5 and MAVS mediate type I interferon responses to coxsackie B virus.
Coxsackie B viruses (CVB) are enteroviruses that have been associated with a variety of human diseases, including myocarditis. In the present study, we found that MDA5 and its adaptor molecule MAVS are critical for type I interferon responses to CVB, since the absence of either MAVS or MDA5 leads to deficient type I interferon production and early mortality in mice infected with CVB. Pancreatic and hepatic necrosis were observed on histopathological examination of MAVS and MDA5 knockout mice infected with CVB. Inflammatory cytokine production in response to systemic CVB infection was independent of MAVS. Surprisingly, virus titers were not elevated in MAVS-deficient mice, despite significant reductions in type I interferon levels. These data highlight the importance of type I interferon in host defense and provide insight on the mechanisms of innate immune responses following coxsackievirus infection.
Wang
Jennifer P
JP
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Jennifer.wang@umassmed.edu
Cerny
Anna
A
Asher
Damon R
DR
Kurt-Jones
Evelyn A
EA
Bronson
Roderick T
RT
Finberg
Robert W
RW
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology*; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology*; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D018345:Mice, Knockout; D019562:Viral Load
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D053487:DEAD-box RNA Helicases; D007370:Interferon Type I; D000072640:Interferon-Induced Helicase, IFIH1; C512612:MAVS protein, mouse; C510592:Ifih1 protein, mouse