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

Various members of the endosomal network fulfil crucial functions in the viral entry, trafficking, and genome release. Rab11 is mainly assigned to recycling endosomes [67] . We made the observation that Rab11-positive vesicles loaded with IFITM3 often carried IAV NP early during infection. Previous reports using live-cell imaging suggested that IFITM3 mediates the directed re-localization of viral particles to lysosomes [77] . Our results argue that the internalization of IAV via recycling endosomes may trap IAV in a non-productive pathway, as the membrane fusion is precluded in recycling endosomes having only a mildly acidic pH of 6.5 [78] . It is conceivable that both mechanisms exist synergistically. In general, viruses being restricted by IFITM3 fuse at a lower pH in late endosomes or lysosomes [51] . IFITM3 on recycling endosomes is thus unlikely to restrict the endosomal entry of IAV (or of other viruses described to be restricted by IFITMs), but may be an important defense against other pathogens entering via recycling endosomes [78] .