Figure 6.

NA contributions to viral release and intercellular movement. (i) Viral mRNAs encoding the membrane proteins NA, HA, and M2 are exported for translation by cytosolic ribosomes. (ii) Exposure of the N-terminal signal sequence (HA) or transmembrane domains (NA and M2) recruits the signal recognition particle (SRP), which (iii) targets the ribosome–nascent chain complex for synthesis at the endoplasmic reticulum (ER). Following synthesis, the proteins oligomerize and are trafficked through the Golgi to the plasma membrane. (iv) Late in replication, the viral ribonucleoproteins (vRNPs) are exported from the nucleus and (v_a) trafficked to the budding regions in the plasma membrane, where (v_b) HA and NA have co-localized, with M2 at the budding boundary. (vi) Following budding, progeny virus can remain associated with the infected cell’s surface through HA binding to sialic acid (SA). (Box A) The envelope protein NA promotes release of the virus from the infected cell surface by hydrolyzing the glycosidic bond attaching the SAs. (vii) SAs present on the glycans of HA and NA can result in HA-mediated virus–virus association. (Box B) NA can separate the viruses by removing these SAs. (viii) In the respiratory tract, the epithelium is protected by mucus, rich in sialylated glycoproteins such as mucin, which can associate with HA and slow viral movement. (Box C) NA can cleave off the SAs from the glycoproteins within the mucus to facilitate movement of the virus to neighboring cells.