Murine gammaherpesvirus-68 glycoprotein B presents a difficult neutralization target to monoclonal antibodies derived from infected mice.
Persistent viruses disseminate from immune hosts. They must therefore resist neutralization by antibody. Murine gammaherpesvirus-68 (MHV-68) represents an accessible model with which to address how resistance to neutralization is achieved and how overcoming it might improve infection control. The MHV-68 glycoprotein B (gB), like that of other herpesviruses, is a virion protein that is essential for infectivity. As such, it presents a potential neutralization target. In order to test whether virus-induced antibodies reduce virion infectivity by binding to gB, monoclonal antibodies (mAbs) were derived from MHV-68-infected mice. gB-specific mAbs were common, but only an IgM specific for the gB N terminus reduced virion infectivity significantly. It inhibited MHV-68 entry into BHK-21 cells at a post-binding step that was linked closely to membrane fusion. Reducing the mAb to IgM monomers compromised neutralization severely, suggesting that a pentameric structure was crucial to its function. Antibody treatment never blocked BHK-21 cell infection completely and blocked the infection of NMuMG epithelial cells hardly at all. Virions saturated with antibody also remained infectious to mice. Thus, the MHV-68 gB presents at best a very difficult target for antibody-mediated neutralization.
Gillet
Laurent
L
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Gill
Michael B
MB
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Colaco
Susanna
S
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Smith
Christopher M
CM
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Stevenson
Philip G
PG
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology* / Q000302:isolation & purification; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology / Q000302:isolation & purification; D008168:Lung / Q000821:virology; D008561:Membrane Fusion; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D018144:Rhadinovirus / Q000276:immunology* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000276:immunology*; D010948:Viral Plaque Assay; D053586:Virus Internalization
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007075:Immunoglobulin M; D014759:Viral Envelope Proteins; C089386:glycoprotein B, murine gammaherpesvirus 68