Interferon response factors 3 and 7 protect against Chikungunya virus hemorrhagic fever and shock
Autor(es): Rudd Penny A, Wilson Jane, Gardner Joy, Larcher Thibaut, Babarit Candice, Le Thuy T, Anraku Itaru, Kumagai Yutaro, Loo Yueh-Ming, Gale Michael, Akira Shizuo, Khromykh Alexander A, Suhrbier Andreas
Resumo: Chikungunya virus (CHIKV) infections can produce severe disease - mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 - 7 (IRF3/7(-/-)) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-?/?) in serum, ?50- - ?10-fold increases in levels of IFN-? - tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, - raised hematocrits. These features are consistent with hemorrhagic shock - were also evident in infected IFN-?/? receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, - keratinocytes in IRF3/7(-/-) mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7(-/-) mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- - TRIF-dependent pathways were primarily responsible for IFN-?/? induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-?/? responses following virus infection can be sufficient to induce hemorrhagic fever - shock, a finding with implications for underst-ing severe CHIKV disease - dengue hemorrhagic fever/dengue shock syndrome.
Imprenta: Journal of Virology, v. 86, n. 18, p. 9888-9898, 2012
Identificador do objeto digital: 10.1128/JVI.00956-12
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Dengue ; Chikungunya virus - Immunology
Data de publicação: 2012
