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

From our findings we assume two putative and presumably additive mechanisms for IFITM3 mediated antiviral action: (i) The first contact with IAV particles after an endocytic uptake in (early) endosomes (role of recycling endosomes is discussed below) triggers the continuous recruitment of pre-existing IFITM3 proteins to IAV containing compartments as a fast antiviral defense in the initial phase of infection. (ii) IFITM3 protein levels are increased by interferon signaling, further propagating its antiviral effect and possibly synergizing with additional IFN-induced antiviral factors [76] . Continuing studies aim to identify the modalities of the direct or indirect interaction between IAV and IFITM3. We have to admit that deficient particles might have the potential to fuse with the plasma membrane but fail to replicate. An abortive and ineffective infection might trigger the IFITM3 activation and recruitment to endosomes in the same way as can be seen for an efficient IAV infection.