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Monoclonal antibodies to the matrix (E1) glycoprotein of mouse hepatitis virus protect mice from encephalitis
J O Fleming1, R A Shubin, M A Sussman
1Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033.
Abstract:
Monoclonal antibodies to the matrix or E1 glycoprotein of mouse hepatitis virus (MHV) were tested for their ability to protect mice from a normally lethal challenge of MHV-4. Four antibodies were tested, and two of these, J.1.3 and J.3.9, were protective. Protection did not correlate with virus neutralization in vitro, antibody isotype, recognition of a unique E1 antigenic site, or dependence on complement in vivo. Survival from acute encephalitis was followed by subacute demyelination, as has been shown with protection mediated by neutralizing monoclonal antibodies against the major glycoprotein, E2. These results demonstrate that antibodies which are specific for a viral matrix protein are able to alter the course of disease.
Insights
Monoclonal antibodies targeting the matrix protein of mouse hepatitis virus (MHV) protected mice from lethal infection. This protection was independent of virus neutralization or complement, highlighting a new therapeutic avenue for viral encephalitis.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Mouse hepatitis virus (MHV) causes lethal encephalitis in mice.
- Monoclonal antibodies (mAbs) targeting viral glycoproteins are investigated for therapeutic potential.
- The role of antibodies against viral matrix proteins in disease modulation is less understood.
Purpose of the Study:
- To evaluate the protective efficacy of monoclonal antibodies against the matrix (M) or E1 glycoprotein of MHV.
- To determine the mechanisms underlying protection mediated by these antibodies.
Main Methods:
- Testing four distinct monoclonal antibodies against MHV M or E1 glycoproteins for protective capacity in mice challenged with MHV-4.
- Assessing protection by monitoring survival and disease progression.
- Analyzing correlation of protection with in vitro virus neutralization, antibody isotype, antigenic site recognition, and complement dependence in vivo.
Main Results:
- Two of the four tested monoclonal antibodies (J.1.3 and J.3.9) conferred significant protection against lethal MHV-4 challenge.
- Protection was not associated with in vitro virus neutralization, antibody isotype, specific E1 epitope recognition, or complement fixation.
- Protected mice experienced survival from acute encephalitis, followed by subacute demyelination, similar to outcomes with anti-E2 glycoprotein antibodies.
Conclusions:
- Monoclonal antibodies specific for the MHV matrix protein can effectively alter the course of MHV-induced disease.
- Antibody-mediated protection against MHV encephalitis can occur independently of virus neutralization.
- These findings suggest that targeting viral matrix proteins with antibodies represents a viable therapeutic strategy for viral central nervous system infections.