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Live Cell Imaging of Alphaherpes Virus Anterograde Transport and Spread
Published on: August 16, 2013
Herpesvirus glycoproteins undergo multiple antigenic changes before membrane fusion
Daniel L Glauser1, Anne-Sophie Kratz, Philip G Stevenson
1Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Plos One
|January 19, 2012
Summary
Murid Herpesvirus-4 (MuHV-4) glycoproteins change conformation during entry, forming a fusogenic structure late in endosomes. These late-stage changes limit antibody effectiveness against herpesvirus fusion.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Herpesvirus entry involves complex interactions of virion glycoproteins and membrane fusion.
- Understanding glycoprotein conformational changes during infection is crucial but remains unclear.
- Previous studies on recombinant glycoproteins offer limited insight into in vivo changes.
Purpose of the Study:
- To investigate in situ conformational changes of Murid Herpesvirus-4 (MuHV-4) entry glycoproteins during infection.
- To determine the timing and nature of these changes relative to viral entry stages.
- To assess the implications of these conformational changes for antibody-mediated neutralization.
Main Methods:
- Utilized conformation-specific monoclonal antibodies for in situ analysis.
- Tracked antigenic changes of MuHV-4 glycoproteins (gB, gH/gL, gp150) during infection.
- Correlated glycoprotein changes with specific stages of viral entry, including membrane fusion.
Main Results:
- MuHV-4 entry machinery components (gB, gH/gL, gp150) exhibit altered antigenicity prior to tegument protein release.
- Further significant antigenic changes occur during the process of membrane fusion.
- Virions adopt their final fusogenic conformation exclusively within late endosomes.
Conclusions:
- Herpesvirus glycoproteins undergo substantial conformational alterations throughout the entry process.
- The fusogenic form of MuHV-4 virions is presented late in endosomes, after initial interactions.
- The distinct antigenic profiles of extracellular versus endosomal virions suggest limited windows for effective antibody blockade of fusion.
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