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

Thomas Morrison, Robert Fraser, Paul Smith, Suresh Mahalingam, Mark Heise

    Research output: Contribution to journalArticle

    68 Citations (Scopus)

    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 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.

    Original languageEnglish
    Pages (from-to)5132-5143
    Number of pages12
    JournalJournal of Virology
    Volume81
    Issue number10
    DOIs
    Publication statusPublished - 2007

    Fingerprint

    Ross River virus
    Virus Diseases
    complement
    animal models
    mice
    Complement Activation
    muscle tissues
    skeletal muscle
    Skeletal Muscle
    arthritis
    Muscles
    Arthritis
    Chikungunya virus
    Alphavirus
    myositis
    tissues
    Osteitis
    synovial fluid
    Myositis
    Synovial Fluid

    Cite this

    Morrison, Thomas ; Fraser, Robert ; Smith, Paul ; Mahalingam, Suresh ; Heise, Mark. / Complement Contributes to Inflammatory Tissue Destruction in a Mouse Model of Ross River Virus-Induced Disease. In: Journal of Virology. 2007 ; Vol. 81, No. 10. pp. 5132-5143.
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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 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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    Complement Contributes to Inflammatory Tissue Destruction in a Mouse Model of Ross River Virus-Induced Disease. / Morrison, Thomas; Fraser, Robert; Smith, Paul; Mahalingam, Suresh; Heise, Mark.

    In: Journal of Virology, Vol. 81, No. 10, 2007, p. 5132-5143.

    Research output: Contribution to journalArticle

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