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Updated: Jul 18, 2026
Measurement of γHV68 Infection in Mice
Published on: November 22, 2011
Murine gammaherpesvirus-68 glycoprotein B presents a difficult neutralization target to monoclonal antibodies derived
Laurent Gillet1, Michael B Gill1, Susanna Colaco1
1Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Abstract:
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.
Insights
Murine gammaherpesvirus-68 (MHV-68) glycoprotein B (gB) is a difficult target for antibody neutralization. A specific IgM antibody targeting the gB N terminus showed limited ability to inhibit viral infectivity.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Persistent viruses must evade antibody neutralization to spread in immune hosts.
- Murine gammaherpesvirus-68 (MHV-68) is a model for studying viral resistance to neutralization.
- Viral glycoprotein B (gB) is essential for infectivity and a potential neutralization target.
Purpose of the Study:
- To investigate if antibodies targeting MHV-68 glycoprotein B (gB) can neutralize viral infectivity.
- To determine the mechanism and efficacy of antibody-mediated neutralization of MHV-68.
- To assess the potential of gB as a target for improved infection control.
Main Methods:
- Generation of monoclonal antibodies (mAbs) against MHV-68 from infected mice.
- Testing the effect of gB-specific mAbs on MHV-68 infectivity and entry into BHK-21 and NMuMG cells.
- Analyzing the role of antibody structure (IgM pentamers vs. monomers) in neutralization.
Main Results:
- gB-specific mAbs were common, but only an N-terminal IgM significantly reduced virion infectivity.
- This IgM inhibited MHV-68 entry at a post-binding step, closely linked to membrane fusion.
- Neutralization was severely compromised when the IgM was reduced to monomers, indicating the importance of its pentameric structure.
- Antibody treatment did not completely block infection in cell lines and failed to block infection in mice.
Conclusions:
- The MHV-68 gB is a challenging target for antibody-mediated neutralization.
- The pentameric structure of IgM is crucial for its limited neutralizing activity against MHV-68.
- Strategies to overcome antibody resistance are needed for effective MHV-68 infection control.
