Models for IFITM3-mediated restriction of IAV infection.

<p>Purple arrows illustrate possible mechanisms of the IAV restriction by IFITM3: direct (Pathway 1) and indirect (Pathway 2) inhibition of transition from hemifusion to full fusion at the limiting membrane of an endosomes, as well as non-productive IAV fusion with ILVs in the absence of back fusion (Pathway 3). Partial dilution/dequenching of viral vDiD upon hemifusion/fusion is shown by lighter red color and full dequenching is shown by light red glow. Alternative endosomal localizations of IFITM3 (limiting membrane vs. ILVs) are shown. Dashed black arrow illustrates possible IAV fusion pathway in cells expressing low, endogenous levels of IFITM3.