Interferon-induced transmembrane protein 3 blocks fusion of sensitive but not resistant viruses by partitioning into virus-carrying endosomes

Suddala, Krishna C.; Lee, Christine C.; Meraner, Paul; Marin, Mariana; Markosyan, Ruben M.; Desai, Tanay M.; Cohen, Fredric S.; Brass, Abraham L.; Melikyan, Gregory B.

LASVpp escape from IFITM3 restriction through virus trafficking and fusion with endosomes lacking this restriction factor. Consistently, LASV GPc-mediated cell-cell fusion is sensitive to IFITM proteins expressed on the surface of target cells. These results highlight the importance of regulation of IFITM trafficking for antiviral activity and offer important clues regarding the determinants of virus resistance to restriction. Of note, the presence of IFITM3 at the sites of IAV fusion does not rule out the possibility that the antiviral effect is due to recruitment of downstream effector proteins, such as ZMPSTE24 [60] . IFITMs have the propensity to heterooligomerize [21] and interact with a number of other proteins [61] , so it is possible that IFITM-driven protein complexes alter the membrane properties and disfavor viral fusion (see below).