In vivo importance of heparan sulfate-binding glycoproteins for murid herpesvirus-4 infection.
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.
Gillet
Laurent
L
Division of Virology, Department of Pathology, University of Cambridge, UK.
May
Janet S
JS
Division of Virology, Department of Pathology, University of Cambridge, UK.
Stevenson
Philip G
PG
Division of Virology, Department of Pathology, University of Cambridge, UK.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000821:virology; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D018144:Rhadinovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D006023:Glycoproteins; D006497:Heparan Sulfate; D011991:Receptors, Virus; D014759:Viral Envelope Proteins