Influenza A Virus Hemagglutinin and Neuraminidase Mutually Accelerate Their Apical Targeting through Clustering of Lipid Rafts

摘要: In polarized epithelial cells, influenza A virus hemagglutinin (HA) and neuraminidase (NA) are intrinsically associated with lipid rafts target the apical plasma membrane for viral assembly budding. Previous studies have indicated that transmembrane domain (TMD) cytoplasmic tail (CT) of HA NA required association rafts, but raft dependencies their targeting controversial. Here, we show coexpression accelerated through accumulation in rafts. was targeted to even when expressed alone, kinetics much slower than infected cells. Coexpression experiments revealed by coexpression. The also M1 not M2. mutations outer leaflet TMD deletion CT reduced abolished acceleration transport, indicating is essential efficient trafficking NA. An situ proximity ligation assay (PLA) were accumulated clustered compartments only both Analysis mutant viruses containing nonraft HA/NA confirmed these findings. We further analyzed markers PLA suggest a possible mechanism transport via clustering rafts. IMPORTANCE Lipid serve as sites entry, particle assembly, budding, leading replication. utilizes virus, key players contain determinants sorting association. However, it remains be elucidated how contribute investigated relation efficiency trafficking. induces accelerates targeting, likely occurs at TGN. This finding provides first evidence two different raft-associated proteins induce clustering, thereby accelerating proteins.