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Low pH deforms the influenza virus envelope
R W Ruigrok1, E A Hewat, R H Wade
1EMBL Grenoble Outstation, France.
Abstract:
Influenza virus membrane fusion is induced by low pH, which triggers an irreversible conformational change in the viral haemagglutinin (HA). The result of this change is the extrusion of the HA fusion peptide, after which it may act in the fusion of virus and endosomal membranes. Here we describe electron microscopic observations on low pH-treated virus after negative staining or cryo-electron microscopy of virus in the frozen hydrated state. The results indicate a destabilization of the virus membrane at low pH that can be reversed by returning the pH to neutral.
Insights
Low pH causes irreversible changes in influenza virus haemagglutinin (HA), extruding its fusion peptide. This destabilizes the virus membrane, a process reversible by returning to neutral pH.
Area of Science:
- Virology
- Structural Biology
- Membrane Biophysics
Background:
- Influenza virus entry into host cells relies on membrane fusion.
- This fusion process is triggered by the viral haemagglutinin (HA) protein.
- Low pH conditions in endosomes initiate conformational changes in HA.
Purpose of the Study:
- To investigate the structural changes in influenza virus at low pH.
- To visualize the effect of low pH on the viral membrane and HA.
- To understand the mechanism of virus-endosome membrane fusion.
Main Methods:
- Negative staining electron microscopy of low pH-treated influenza virus.
- Cryo-electron microscopy of influenza virus in a frozen hydrated state.
- Observation of structural alterations induced by pH changes.
Main Results:
- Low pH induces significant destabilization of the influenza virus membrane.
- Conformational changes in haemagglutinin (HA) lead to fusion peptide extrusion.
- The observed membrane destabilization is reversible upon return to neutral pH.
Conclusions:
- Low pH is critical for initiating irreversible conformational changes in HA, essential for viral fusion.
- The study provides direct visualization of virus membrane destabilization at low pH.
- Understanding these pH-dependent structural dynamics is key to viral entry mechanisms.