Glycoprotein B switches conformation during murid herpesvirus 4 entry

J Gen Virol. 2008 Jun;89(Pt 6):1352-1363. doi: 10.1099/vir.0.83519-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Glycoproteins / metabolism*
  • Herpesviridae Infections / virology*
  • Humans
  • Mice
  • Neutralization Tests
  • Protein Conformation
  • Rhadinovirus / chemistry
  • Rhadinovirus / physiology*
  • Tumor Virus Infections / virology*
  • Viral Proteins / metabolism*
  • Virus Attachment


  • Antibodies, Viral
  • Glycoproteins
  • Viral Proteins