Interaction of influenza virus hemagglutinin with a lipid monolayer. A comparison of the surface activities of intact virions, isolated hemagglutinins, and a synthetic fusion peptide.

In the infectious entry pathway of influenza virus, the low pH of the endosomal compartment induces an irreversible conformational change in influenza virus hemagglutinin, leading to fusion of viral and endosomal membranes. In the current report, we characterized the low-pH-induced activation of hemagglutinin of influenza strain X31 by studying its interaction with a lipid monolayer. The surface activities of virions, of isolated hemagglutinins and its proteolytic fragments, and of a synthetic peptide mimicking the amino terminus of subunit 2 of hemagglutinin are compared. The data indicate that the surface activity of both virions and isolated hemagglutinin develop as a result of the low-pH-induced conformational change in hemagglutinin. The surface activity of isolated hemagglutinin is mainly caused by penetration into the lipid monolayer of protein domains other than the amino terminus of subunit 2 of hemagglutinin; domains in subunit 1 may be involved. The surface activity of virions appears to be a secondary effect of the conformational change and is explained by assuming a net transfer of viral lipids to the lipid monolayer.