Molecular Mechanisms Involved in the Pathogenesis of Alphavirus-Induced Arthritis

Figure 1

Pathogenesis of alphavirus-induced arthritis/myositis. After inoculation through the bite of an infected mosquito in the skin, alphaviruses disseminate in the host organism through the bloodstream. Liver, spleen, muscle, and lymph nodes are sites of primary replication, allowing an efficient virus spread. Langerhans cells facilitate virus delivery to the lymph nodes. Interferon (IFN) program is early activated, but the alphaviruses developed several mechanisms to inhibit this antiviral response. The acute phase of the disease involves virus replication followed by an inflammatory response in the target tissues, which is characterized by an extensive infiltration of lymphocytes, NK cells, neutrophils, and macrophages (the main component). The increase in the levels of several proinflammatory cytokines and chemokines in the site of infection and in the plasma is associated with myositis and arthralgia/arthritis. Also, the secretion of metalloproteinases (MMP) in the joint tissue may contribute to articular damage. Persistence of the symptoms may be related to the persistence of the virus or its products in the target cells with the subsequent accumulation of inflammatory mediators such as IL-6 and GM-CSF. A question that remains open is whether an autoimmune process is associated to the persistence of the inflammatory response, as observed for rheumatoid arthritis.