Complement contributes to inflammatory tissue destruction in a mouse model of Ross River virus-induced disease

Autor(es): Morrison Thomas E, Fraser Robert J, Smith Paul N, Mahalingam Suresh, Heise Mark T


Resumo: Arthritogenic alphaviruses, including Ross River virus (RRV) - chikungunya virus, are mosquito-borne viruses that cause significant human disease worldwide, including explosive epidemics that can result in thous-s 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, - 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 - 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 - C3(-/-) mice had similar numbers - 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 - mice infected with RRV - suggest that complement plays an essential role in the effector phase, but not the inductive phase, of RRV-induced arthritis - myositis.


Imprenta: Journal of Virology, v. 81, n. 10, p. 5132-5143, 2007


Identificador do objeto digital: 10.1128/JVI.02799-06


Descritores: Chikungunya virus - Biochemistry ; Chikungunya virus - Cytopathology ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Immune response ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya virus - Clinical examination ; Chikungunya Virus - Virus ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology


Data de publicação: 2007