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.

In addition to tracking IAV particles that co-traffic with IFITM3+ compartments for an extended period of time, transient encounters with IFITM3+ compartments that did not inhibit subsequent IAVpp fusion were also observed. An example trace of an IAV pseudovirus shows a brief (~40 sec) apparent co-localization with an IFITM3+ compartment at around 23 minutes (Fig 3G and 3H , S6 Movie). Examination of 3D trajectories demonstrate that the particle does not significantly colocalize/co-traffic with the IFITM3+ endosome and that fusion occurs at around 31 minutes with no above-background IFITM3-imTFP1 signal (Fig 3H and The viral particle appears to transiently colocalize with an IFITM3+ endosome when visualized in 2D, but particle tracking performed in 3D shows that the viral particle and the IFITM3+ endosome traffic in different Z-planes. These observations suggest that a transient and chance encounter of a virus carrying endosome with an IFITM3+ endosome is not sufficient to restrict fusion. In contrast, fusion is blocked after sustained and prolonged IAVpp co-trafficking with an IFITM3+ endosome, which strongly implies that the virus is being carried by an IFITM3-enriched compartment.