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Molecular basis of rabies virus virulence. II. Identification of a site on the CVS glycoprotein associated with
Abstract:
Nine anti-G monoclonal antibodies were used to select mutants of the CVS strain of rabies virus resistant to neutralization. Seven mutants were avirulent in adult mice and two others exhibited an attenuated pathogenicity. Both categories were resistant to monoclonal antibodies 194-2 and 248-8. Virulence appears to be associated with a particular configuration of a region of the glycoprotein which is located at the intersection of the epitopes recognized by these two monoclonal antibodies. Our results confirm the role played by the glycoprotein in the neurovirulence of rabies virus.
Insights
Researchers identified specific rabies virus (CVS strain) mutations affecting glycoprotein structure, leading to reduced virulence in mice. These findings highlight the glycoprotein's crucial role in rabies virus neurovirulence.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Rabies virus glycoprotein (G) is critical for viral entry and pathogenesis.
- Neutralizing monoclonal antibodies (mAbs) targeting the G protein are essential tools for studying rabies virus virulence.
Purpose of the Study:
- To investigate the relationship between G protein structure and rabies virus neurovirulence.
- To identify specific G protein epitopes associated with viral pathogenicity.
Main Methods:
- Selection of rabies virus CVS strain mutants resistant to neutralization by anti-G mAbs.
- Assessment of mutant avirulence and pathogenicity in adult mice.
- Characterization of G protein epitopes recognized by specific mAbs (194-2 and 248-8).
Main Results:
- Seven avirulent and two attenuated rabies virus mutants were isolated.
- All selected mutants exhibited resistance to mAbs 194-2 and 248-8.
- Virulence correlated with a specific G protein configuration at the intersection of epitopes for mAbs 194-2 and 248-8.
Conclusions:
- The study confirms the significant role of the rabies virus G protein in neurovirulence.
- Specific structural configurations within G protein epitopes influence viral pathogenicity.
- Targeting these G protein regions may offer strategies for rabies virus attenuation.