A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection

Ranjbar, Shahin; Haridas, Viraga; Jasenosky, Luke D.; Falvo, James V.; Goldfeld, Anne E.

Successful intracellular pathogens often use strategies to gain access to cellular compartments required for their survival ahead of the initiation of innate host antimicrobial mechanisms. The well-characterized interferon (IFN)-induced transmembrane (IFITM) gene family encodes highly conserved proteins that act at early steps post-viral entry, thereby precluding establishment of productive infection (Diamond and Farzan, 2013) . In humans, three IFITMs (IFITM1, IFITM2, and IFITM3) are widely expressed, and the genes encoding these restriction factors are activated by types I and II IFN stimulation via IFN-sensitive response elements (ISREs) in their regulatory regions (Ackrill et al., 1991; Friedman et al., 1984; Kelly et al., 1985; Lewin et al., 1991; Reid et al., 1989) . While IFITM1-3 share substantial sequence similarity, IFITM1 primarily is found at the cell periphery due to its lack of an N-terminal 21 amino acid sequence that promotes IFITM2 and IFITM3 recruitment to late endosomal/lysosomal membranes (Jia et al., 2012; John et al., 2013; Weston et al., 2014) .