Assembly of Viral Components at the Budding Site

Assembly of Viral Components at the Budding Site Following synthesis on membrane-bound ribosomes, the three viral integral membrane proteins, HA (hemagglutinin), NA (neuraminidase) and M2 (ion channel) enter the host endoplasmic reticulum (ER) where all three are folded and HA and NA are glycosylated. Subsequently HA is assembled into a trimer. HA, NA and M2 are transported to the Golgi apparatus where cysteine residues on HA and M2 are palmitoylated. Furin cleaves HA into HA1 and HA2 subunits and all three proteins are directed to the virus assembly site on the apical plasma membrane via apical sorting signals. The signals for HA and NA reside on the transmembrane domains (TMD) while the sorting signal for M2 is not yet characterized. The TMDs of HA and NA also contain the signals for lipid raft association. Lipid rafts are non-ionic detergent-resistant lipid microdomains within the plasma membrane that are rich in sphingolipids and cholesterol. Examination of purified virus particles indicates that influenza virus buds preferentially from these microdomains.