A balancing act between IFITM3 and IRF3

Interferon(IFN)-induced transmembrane protein 3(IFITM3)is a potent antiviral factor capable of restricting numerous virus infections.1 Viruses inhibited by IFITM3 generally enter cells via endocytosis,and are trafficked to IFITM3-positive intracellular membrane compartments.1,2 IFITM3-positive compartments are acidic and stain positive for a variety of endosomal,lysosomal and autophagosomal markers.2,3 Although the membrane fusion of many endocytic viruses,such as influenza virus,is triggered by acidic pH,fusion is blocked in the presence of IFITM3,and virions are degraded2,4,5(Figure 1).It has been proposed that IFITM3 alters membrane properties,including rigidity and curvature,to inhibit virus membrane fusion.5 The molecular mechanism underlying these IFITM3-induced membrane alterations is not well characterized,and whether IFITM3 has other cellular functions is also not known.