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

A semi-automated image analysis of IAV A/HK/1/68 (pdmH3N2) and IAV A/R/D6/2009 (pdmH1N1) infected A549 cells revealed IFITM3 clustering early after infection in both cases, with few differences in kinetics, which may reflect strain specific replication kinetics [73] . The CD225 domain of IFITM3, which is composed of the intermembrane domain 1 and the intracellular loop, contains two phenylalanine residues mediating the physical association between IFITMs; these residues are strongly connected with the antiviral function [39] . Combining this finding with our observation of the increasing levels of larger IFITM3 clusters, we suggest a direct relation between cluster formation and IFITM3`s antiviral activity on endosomal vesicles. The IFITM3 clustering on apparently vesicular structures started early after infection (3-5 h p.i.), with an initial co-localization of IFITM3 with an early endosomal marker and a later co-localization with a late endosomal marker, reflecting the early to late endosomal pathway of IAV. It appears likely, therefore, that IFITM3