Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction

Lin, Tsai-Yu; Chin, Christopher R.; Everitt, Aaron R.; Clare, Simon; Perreira, Jill M.; Savidis, George; Aker, Aaron M.; John, Sinu P.; Sarlah, David; Carreira, Erick M.; Elledge, Stephen J.; Kellam, Paul; Brass, Abraham L.

We note, however, that AmphoB did little to alleviate either IFITM1's antiviral action or it's inhibitory effect on membrane fluidity and cell-to-cell fusion. Therefore, additional efforts will be needed to determine if the effect of IFITM1 on plasma membrane fluidity is the same as the effect of IFITM3 on endosomal membranes and if AmphoB's antagonism of IFITM3 results from alterations in membrane fluidity. In this regard, we are unsure as to why AmphoB specifically overcomes IFITM2 and IFITM3 while leaving IFITM1's actions predominantly extant. One factor may be proximity, because AmphoB is endocytosed quite rapidly leading to its concentration in the late endosomes and lysosomes, the areas of IFITM3's highest concentrations. Future studies using derivatives of AmphoB and IFITM mutant proteins will be useful in further testing such models.