Figure 7.

A model for the function of NS3 based on its membrane residency and known topology. (1) The host protein p11 is present in cells with p36 as part of the annexin II complex involved in cellular exocytosis. (2) NS3 is synthesized in the infected cell and localizes to the secretory pathway, where it engages with p11 either alone or in a partial annexin II complex by the displacement of one copy of p36 via a sequence at the N terminus. (3) Assembled virions formed in cytosolic virosomes similarly bind to NS3 via interaction between virion protein VP2 and a sequence in the NS3 carboxyl domain. (4) By virtue of the interactions, the assembled virions are drawn into contact with the p11/annexin II complex and engage to cellular exocytic machinery to affect nonlytic virus release.