Effects of low pH on influenza virus. Activation and inactivation of the membrane fusion capacity of the hemagglutinin

The hemagglutinin of influenza virus undergoes a conformational change at low pH, which results in exposure of a hydrophobic segment of the molecule, crucial to expression of viral fusion activity. We have studied the effects of incubation of the virus at low pH either at 37 or 0 degrees C. Treatmen...

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Bibliographic Details
Published in:The Journal of biological chemistry 1987-12, Vol.262 (36), p.17744-17749
Main Authors: Stegmann, T, Booy, F P, Wilschut, J
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Membrane
Cell membranes. Ionic channels. Membrane pores
Cell structures and functions
Fundamental and applied biological sciences. Psychology
hemagglutinins
Hemagglutinins, Viral
Hydrogen-Ion Concentration
influenza virus
Microscopy, Electron
Molecular and cellular biology
Orthomyxoviridae
Osmolar Concentration
Protein Conformation
Temperature
Viral Fusion Proteins
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Summary:The hemagglutinin of influenza virus undergoes a conformational change at low pH, which results in exposure of a hydrophobic segment of the molecule, crucial to expression of viral fusion activity. We have studied the effects of incubation of the virus at low pH either at 37 or 0 degrees C. Treatment of the virus alone at pH 5.0 induces the virus particles to become hydrophobic, as assessed by measuring the binding of zwitterionic liposomes to the virus. At 37 degrees C this hydrophobicity is transient, electron microscopic examination of the virus reveals a highly disorganized spike layer, and fusion activity toward ganglioside-containing zwitterionic liposomes, measured at 37 degrees C with a kinetic fluorescence assay, is irreversibly lost. By contrast, after preincubation of the virus alone at pH 5.0 and 0 degrees C fusion activity remains unaffected. Yet, the preincubation at 0 degrees C does result in exposure of the hydrophobic segment of hemagglutinin, but now hydrophobicity is sustained and viral spike morphology unaltered. Hydrophobicity also remains to a significant extent upon pH neutralization, but fusion activity is negligible under these conditions. It is concluded that for optimal expression of fusion activity the virus must be bound to the target membrane before exposure to low pH. Furthermore, even after exposure of the hydrophobic segment of hemagglutinin, fusion occurs only at low pH. Finally, fusion occurs only at elevated temperature, possibly reflecting the unfolding of hemagglutinin trimers or the cooperative action of several hemagglutinin trimers in the reaction.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)45442-7