In vivo importance of heparan sulfate-binding glycoproteins for murid herpesvirus-4 infection

J Gen Virol. 2009 Mar;90(Pt 3):602-613. doi: 10.1099/vir.0.005785-0.


Many herpesviruses bind to heparan sulfate (HS). Murid herpesvirus-4 (MuHV-4) does so via its envelope glycoproteins gp70 and gH/gL. MuHV-4 gp150 further regulates an HS-independent interaction to make that HS-dependent too. Cell binding by MuHV-4 virions is consequently strongly HS-dependent. Gp70 and gH/gL show some in vitro redundancy: an antibody-mediated blockade of HS binding by one is well tolerated, whereas a blockade of both severely impairs infection. In order to understand the importance of HS binding for MuHV-4 in vivo, we generated mutants lacking both gL and gp70. As expected, gL(-)gp70(-) MuHV-4 showed very poor cell binding. It infected mice at high dose but not at low dose, indicating defective host entry. But once entry occurred, host colonization, which for MuHV-4 is relatively independent of the infection dose, was remarkably normal. The gL(-)gp70(-) entry deficit was much greater than that of gL(-) or gp70(-) single knockouts. And gp150 disruption, which allows HS-independent cell binding, largely rescued the gL(-)gp70(-) cell binding and host entry deficits. Thus, it appeared that MuHV-4 HS binding is important in vivo, principally for efficient host entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • Female
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Heparitin Sulfate / metabolism*
  • Kidney / cytology
  • Kidney / virology
  • Mice
  • NIH 3T3 Cells
  • Protein Binding
  • Receptors, Virus / metabolism*
  • Rhadinovirus / genetics
  • Rhadinovirus / metabolism
  • Rhadinovirus / pathogenicity*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*


  • Glycoproteins
  • Receptors, Virus
  • Viral Envelope Proteins
  • Heparitin Sulfate