Interferon regulatory factor 3 attenuates reovirus myocarditis and contributes to viral clearance.

Holm GH, Pruijssers AJ, Li L, Danthi P, Sherry B, Dermody TS
J Virol. 2010 84 (14): 6900-8

PMID: 20463082 · PMCID: PMC2898218 · DOI:10.1128/JVI.01742-09

Apoptosis is a pathological hallmark of encephalitis and myocarditis caused by reovirus in newborn mice. In cell culture models, the antiviral transcription factor interferon regulatory factor 3 (IRF-3) enhances reovirus-induced apoptosis following activation via retinoic acid inducible gene I and interferon promoter-stimulating factor 1. To determine the role of IRF-3 in reovirus disease, we infected newborn IRF-3(+/+) and IRF-3(-/-) mice perorally with mildly virulent strain type 1 Lang (T1L) and fully virulent strain type 3 SA+ (T3SA+) and monitored infected animals for survival. Both wild-type and IRF-3(-/-) mice succumbed with equivalent frequencies to infection with T3SA+. However, the absence of IRF-3 was associated with significantly decreased survival rates following infection with T1L. The two virus strains achieved similar peak titers in IRF-3(+/+) and IRF-3(-/-) mice in the intestine, brain, heart, liver, and spleen. However, by day 12 postinoculation, titers in all organs examined were 10- to 100-fold higher in IRF-3(-/-) mice than those in wild-type mice. Increased titers were associated with marked pathological changes in all organs examined, especially in the heart, where absence of IRF-3 resulted in severe myocarditis. Cellular and humoral immune responses were equivalent in wild-type and IRF-3(-/-) animals, suggesting that IRF-3 functions independently of the adaptive immune response to enhance reovirus clearance. Thus, IRF-3 serves to facilitate virus clearance and prevent tissue injury in response to reovirus infection.

MeSH Terms (18)

Animals Animals, Newborn Cells, Cultured Humans Immunity Interferon-beta Interferon Regulatory Factor-3 Liver Mice Mice, Inbred C57BL Mice, Knockout Myocarditis Myocytes, Cardiac Reoviridae Reoviridae Infections Spleen Survival Rate Tissue Distribution

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