ID: 119: FAF1 regulates the type I interferon signaling against RNA virus infection

Abstract

Fas-associated factor-1 (FAF1) is a component of the death-inducing signaling complex in Fas-mediated apoptosis and regulates NF-kb activity as well as ubiquitination and proteaomal degradation. In this study, we show that FAF1 modulate NF- κ b and Type I interferon pathway as a positive regulator. Overexpression of FAF1 in various cell types enhances the production of inflammatory cytokines and Type I interferons upon Vesicular Stomatitis virus, Influenza A virus or Newcastle disease virus infection. Controversially, knockdown of FAF1 in raw 264.7 cells, MEF cells or BMDM cells derived from FAF1gt/gt mice markedly enhances susceptibility to RNA virus infection and shows lower level of inflammatory cytokines and type I interferon production. Consistent with in vitro results, upon infection of Vesicular Stomatitis virus (Indiana strain), FAF1gt/gt mice exhibited marked susceptibility to virus infection and decreased level of IFN- β and IL-6 from serum. These findings suggest that FAF1 is a positive regulator that modulates the NF- κ B and Type I interferon signaling pathway against RNA virus infection. [This research was supported by Grant No. 2015020957 from the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology].