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  • Complement Contributes to Inflammatory Tissue Destruction in a Mouse Model of Ross River Virus-Induced Disease

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    Author(s)
    E. Morrison, Thomas
    J. Fraser, Robert
    N. Smith, Paul
    Mahalingam, Suresh
    T. Heise, Mark
    Griffith University Author(s)
    Mahalingam, Suresh
    Year published
    2007
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    Abstract
    Arthritogenic alphaviruses, including Ross River virus (RRV) and chikungunya virus, are mosquito-borne viruses that cause significant human disease worldwide, including explosive epidemics that can result in thousands to millions of infected individuals. Similar to infection of humans, infection of C57BL/6 mice with RRV results in severe monocytic inflammation of bone, joint, and skeletal muscle tissues. We demonstrate here that the complement system, an important component of the innate immune response, enhances the severity of RRV-induced disease in mice. Complement activation products were detected in the inflamed tissues ...
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    Arthritogenic alphaviruses, including Ross River virus (RRV) and chikungunya virus, are mosquito-borne viruses that cause significant human disease worldwide, including explosive epidemics that can result in thousands to millions of infected individuals. Similar to infection of humans, infection of C57BL/6 mice with RRV results in severe monocytic inflammation of bone, joint, and skeletal muscle tissues. We demonstrate here that the complement system, an important component of the innate immune response, enhances the severity of RRV-induced disease in mice. Complement activation products were detected in the inflamed tissues and in the serum of RRV-infected wild-type mice. Furthermore, mice deficient in C3 (C3-/-), the central component of the complement system, developed much less severe disease signs than did wild-type mice. Complement-mediated chemotaxis is essential for many inflammatory arthritides; however, RRV-infected wild-type and C3-/- mice had similar numbers and composition of inflammatory infiltrates within hind limb skeletal muscle tissue. Despite similar inflammatory infiltrates, RRV-infected C3-/- mice exhibited far less severe destruction of skeletal muscle tissue. In addition to these studies, complement activation was also detected in synovial fluid from RRV-infected patients. Taken together, these findings indicate that complement activation occurs in the tissues of humans and mice infected with RRV and suggest that complement plays an essential role in the effector phase, but not the inductive phase, of RRV-induced arthritis and myositis.
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    Journal Title
    Journal of Virology
    Volume
    81
    Issue
    10
    DOI
    https://doi.org/10.1128/JVI.02799-06
    Copyright Statement
    © 2007 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
    Subject
    Microbiology not elsewhere classified
    Biological Sciences
    Agricultural and Veterinary Sciences
    Medical and Health Sciences
    Publication URI
    http://hdl.handle.net/10072/54976
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