Glycoprotein B switches conformation during murid herpesvirus 4 entry

Gillet, Laurent, Colaco, Susanna and Stevenson, Philip G. (2008) Glycoprotein B switches conformation during murid herpesvirus 4 entry. Journal of General Virology, 89 6: 1352-1363. doi:10.1099/vir.0.83519-0


Author Gillet, Laurent
Colaco, Susanna
Stevenson, Philip G.
Title Glycoprotein B switches conformation during murid herpesvirus 4 entry
Journal name Journal of General Virology   Check publisher's open access policy
ISSN 0022-1317
1465-2099
Publication date 2008
Sub-type Article (original research)
DOI 10.1099/vir.0.83519-0
Open Access Status
Volume 89
Issue 6
Start page 1352
End page 1363
Total pages 12
Place of publication Reading, Berks, United Kingdom
Publisher Society for General Microbiology
Language eng
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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