IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells

Kummer, Susann; Avinoam, Ori; Kräusslich, Hans-Georg

Genome-wide siRNA screens have identified many host factors modulating influenza virus infection [28] [29] [30] [31] [32] . Brass et al., 2009 [32] and Shapira et al., 2009 [33] reported the strong inhibition of IAV infection by interferon-induced transmembrane proteins (IFITMs). The IFITM variants 1-3 can be induced by interferon I and II. Their localization is cell type-or tissue-dependent and changes with the expression level with a preference for cytoplasmic vesicles in most monolayer cell lines [34] [35] [36] [37] [38] . Besides IAV, IFITM proteins have also been reported to confer a basal resistance to members of the Flaviviridae (Dengue and West Nile Virus) [39] , Bunyaviridae (Rift Valley Fever Virus) [40] , Filoviridae (Ebola Virus) [41] , Coronaviridae (SARS) and Retroviridae (HIV) [32] , showing an unusually broad activity against a wide variety of enveloped and some non-enveloped viruses [32] . However, murine leukemia virus (MLV) is not restricted by IFITM3 despite being an enveloped virus [32] . The relevance of the IFITM3-mediated inhibition of IAV infection received strong support when it was shown that IFITM3 polymorphisms correlated with the severity of IAV disease in human infection [42] . The relevance of the IFITM3 rs12252-C polymorphism for severe IAV infection appears to be population-dependent [43] [44] [45] [46] [47] [48] , and a second IFITM3 single nucleotide polymorphism, rs34481144-A, was also reported to influence the severity of IAV infection in humans [49] . However, the mechanism of the IFITM-mediated inhibition of IAV infection remains under discussion.