The role of antibody in recovery from alphavirus encephalitis

Authors

  • Diane Griffin,

    Corresponding author
    1. Diane Griffin1, Beth Levine2, William Tyor1, Sukathida Ubol4, Philippe Despres5, 1Department of Molecular Microbiology and Immunology. Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland. USA. 2Department of Medicine, Columbia University College of Physicians and Surgeons. New York City, New York, USA, 3Department of Neurology, Medical University of South Carolina, Charleston. South Carolina, USA. 4Department of Microbiology, Mahidol University, Bangkok, Thailand, 5Unité des Arbovirus at Virus des Fièvres Hémorragique.s. Institut Pasteur. Paris, France.
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  • Beth Levine,

    1. Diane Griffin1, Beth Levine2, William Tyor1, Sukathida Ubol4, Philippe Despres5, 1Department of Molecular Microbiology and Immunology. Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland. USA. 2Department of Medicine, Columbia University College of Physicians and Surgeons. New York City, New York, USA, 3Department of Neurology, Medical University of South Carolina, Charleston. South Carolina, USA. 4Department of Microbiology, Mahidol University, Bangkok, Thailand, 5Unité des Arbovirus at Virus des Fièvres Hémorragique.s. Institut Pasteur. Paris, France.
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  • William Tyor,

    1. Diane Griffin1, Beth Levine2, William Tyor1, Sukathida Ubol4, Philippe Despres5, 1Department of Molecular Microbiology and Immunology. Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland. USA. 2Department of Medicine, Columbia University College of Physicians and Surgeons. New York City, New York, USA, 3Department of Neurology, Medical University of South Carolina, Charleston. South Carolina, USA. 4Department of Microbiology, Mahidol University, Bangkok, Thailand, 5Unité des Arbovirus at Virus des Fièvres Hémorragique.s. Institut Pasteur. Paris, France.
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  • Sukathida Ubol,

    1. Diane Griffin1, Beth Levine2, William Tyor1, Sukathida Ubol4, Philippe Despres5, 1Department of Molecular Microbiology and Immunology. Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland. USA. 2Department of Medicine, Columbia University College of Physicians and Surgeons. New York City, New York, USA, 3Department of Neurology, Medical University of South Carolina, Charleston. South Carolina, USA. 4Department of Microbiology, Mahidol University, Bangkok, Thailand, 5Unité des Arbovirus at Virus des Fièvres Hémorragique.s. Institut Pasteur. Paris, France.
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  • Philippe Desprès

    1. Diane Griffin1, Beth Levine2, William Tyor1, Sukathida Ubol4, Philippe Despres5, 1Department of Molecular Microbiology and Immunology. Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland. USA. 2Department of Medicine, Columbia University College of Physicians and Surgeons. New York City, New York, USA, 3Department of Neurology, Medical University of South Carolina, Charleston. South Carolina, USA. 4Department of Microbiology, Mahidol University, Bangkok, Thailand, 5Unité des Arbovirus at Virus des Fièvres Hémorragique.s. Institut Pasteur. Paris, France.
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Diane E, Griffia Johns Hopkins University School of Public Health Room E5132 61S N. Wolfe St, Baltimore MD 21205 USA Fax: 1 410 955 0105 USA e-mail: dgriffin@welchlink.welch.jhu.edu

Summary

Alphaviruses infect neurons in the brain and spinal cord and cause acute encephalomyelitis in a variety of mammals. The outcome of infection is determined by whether the neurons survive infection and this, in turn, is determined by the virulence of the virus and the age of the host at the time of infection. We have been studying Sindbis virus (SV) infection i of mice as a model system for alphavirus-induced encephalomyelitis. Investigation of intracerebral infection of weanling mice with two different strains of SV bas allowed us to analyze the role of the immune response in protection from fatal disease virulent NSV strain) and in CLEARANCE of virus from the nervous system during non-fatal disease (less virulent SV AR339 strain). Neutralizing and non-neutralizing antibodies to the El and E2 surface glycoproteins can protect mice from fatal NSV infection when given before or after infection, while T cells are not protective, The mechanism of antibody-mediated protection is not known, but it is likely that more than one mechanism Is involved and that different mechanisms are involved in pre-infection and post-infection treatment protection. Clearance of infectious virus from the nervous system of mice during recovery from non-fatal disease is accomplished by antibodies to the E2 glycoprotein. The process does not involve damage to the infected neurons and is independent of complement and mononuclear cells. Bivalent antibody is required and binds to the surface of the infected cell. Initially, release of virus by budding from the cell surface is prevented and, subsequently, intracellular virus replication is inhibited possibly through antiviral mechanisms induced in co-operation with interferon. This non lytic mechanism for control of virus infection results in the prolonged presence of viral RNA in tissue and the need for prolonged intrathecal synthesis of antiviral antibody by B cells within the central nervous system.

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