Interaction of influenza virus hemagglutinin with target membrane lipids is a key step in virus-induced hemolysis and fusion at pH 5.2.
The molecular mechanism of hemolysis and fusion by influenza virus in acidic media was studied. First, the effect of trypsin treatment on the activity of fibroblast-grown influenza virus was studied. The results showed that the split form of viral hemagglutinin, HA1 and HA2, but not the precursor, is responsible for the activity. Second, the interaction of egg-grown influenza virus, which contains the split hemagglutinin, with lipid liposomes was studied by spin labeling and electron microscopy. Phospholipid transfer from the viral envelope to the lipid bilayer membrane occurred within 30 s at pH 4.5-5.4. The transfer is largely independent of the lipid composition and the crystalline vs. liquid/crystalline state of the membrane. Virus-induced lysis of liposomes also took place rapidly in the same pH range. Envelope fusion with liposomes occurred at pH 5.2 but not at pH 7.0. These characteristic interactions were similar to those between influenza virus and erythrocytes reported previously. On the other hand, hemagglutinating virus of Japan did not interact with liposomes at neutral pH. These results suggest that protonation of the NH2-terminal segment of the HA2 form causes interaction of the segment with the lipid core of the target cell membrane, leading to hemolysis and fusion.
D002459:Cell Fusion / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology*; D006389:Hemagglutinins, Viral / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus; D008081:Liposomes; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D013113:Spin Labels; D013329:Structure-Activity Relationship
D006389:Hemagglutinins, Viral; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D013113:Spin Labels