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PLoS Pathog. 2017 May 22;13(5):e1006398. doi: 10.1371/journal.ppat.1006398. eCollection 2017 May.

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

Author information

1
College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
2
Faculty of Veterinary & Animal Science, Sylhet Agricultural University, Sylhet, Bangladesh.
3
College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon, Korea.
4
Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea.
5
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, California, United States of America.

Abstract

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.

PMID:
28542569
PMCID:
PMC5456407
DOI:
10.1371/journal.ppat.1006398
[Indexed for MEDLINE]
Free PMC Article

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