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Glycoprotein B switches conformation during murid herpesvirus 4 entry.

Authors
  • Gillet, Laurent1
  • Colaco, Susanna
  • Stevenson, Philip G
  • 1 Division of Virology, Department of Pathology, University of Cambridge, UK.
Type
Published Article
Journal
The Journal of general virology
Publication Date
June 2008
Volume
89
Issue
Pt 6
Pages
1352–1363
Identifiers
DOI: 10.1099/vir.0.83519-0
PMID: 18474550
Source
Medline
License
Unknown

Abstract

Herpesviruses are ancient pathogens that infect all vertebrates. The most conserved component of their entry machinery is glycoprotein B (gB), yet how gB functions is unclear. A striking feature of the murid herpesvirus 4 (MuHV-4) gB is its resistance to neutralization. Here, we show by direct visualization of infected cells that the MuHV-4 gB changes its conformation between extracellular virions and those in late endosomes, where capsids are released. Specifically, epitopes on its N-terminal cell-binding domain become inaccessible, whilst non-N-terminal epitopes are revealed, consistent with structural changes reported for the vesicular stomatitis virus glycoprotein G. Inhibitors of endosomal acidification blocked the gB conformation switch. They also blocked capsid release and the establishment of infection, implying that the gB switch is a key step in entry. Neutralizing antibodies could only partially inhibit the switch. Their need to engage a less vulnerable, upstream form of gB, because its fusion form is revealed only in endosomes, helps to explain why gB-directed MuHV-4 neutralization is so difficult.

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