FAS-associated factor-1 positively regulates type I interferon response to RNA virus infection by targeting NLRX1

• Published in: PLoS pathogens Vol. 13; no. 5; p. e1006398
• Main Authors: Kim, Jae-Hoon, Park, Min-Eun, Nikapitiya, Chamilani, Kim, Tae-Hwan, Uddin, Md Bashir, Lee, Hyun-Cheol, Kim, Eunhee, Ma, Jin Yeul, Jung, Jae U., Kim, Chul-Joong, Lee, Jong-Soo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2017; Public Library of Science (PLoS)
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Animals; Apoptosis; Apoptosis Regulatory Proteins; Biology and Life Sciences; Carrier Proteins - genetics; Carrier Proteins - immunology; Cellular signal transduction; Cytokines; Death; Degradation; Development and progression; Fas antigen; Female; Genetic aspects; Humans; Immune system; Infections; Inflammation; Interferon; Interferon Type I - genetics; Interferon Type I - immunology; Intracellular Signaling Peptides and Proteins; Kinases; Macrophages - immunology; Macrophages - virology; Male; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondrial Proteins - genetics; Mitochondrial Proteins - immunology; Mortality; NF-kappa B - genetics; NF-kappa B - immunology; NF-κB protein; Physiological aspects; Proteasomes; Research and Analysis Methods; Ribonucleic acid; RNA; RNA virus infections; RNA Virus Infections - genetics; RNA Virus Infections - immunology; RNA Virus Infections - virology; RNA viruses; RNA Viruses - physiology; Ubiquitination; Veterinary colleges; Viruses; Bangladesh; South Korea
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006398

FAS-associated factor-1 (FAF1) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis. It regulates NF-κB activity, ubiquitination, and proteasomal degradation. Here, we found that FAF1 positively regulates the type I interferon pathway. FAF1gt/gt mice, which deficient in FAF1, and FAF1 knockdown immune cells were highly susceptible to RNA virus infection and showed low levels of inflammatory cytokines and type I interferon (IFN) production. FAF1 was bound competitively to NLRX1 and positively regulated type I IFN signaling by interfering with the interaction between NLRX1 and MAVS, thereby freeing MAVS to bind RIG-I, which switched on the MAVS-RIG-I-mediated antiviral signaling cascade. These results highlight a critical role of FAF1 in antiviral responses against RNA virus infection.