Virus dissemination and target organs.

Following inoculation with CHIKV through a mosquito bite, the virus directly enters the subcutaneous capillaries, with some viruses infecting susceptible cells in the skin, such as macrophages or fibroblasts and endothelial cells. Local viral replication seems to be minor and limited in time, with the locally produced virus probably being transported to secondary lymphoid organs close to the site of inoculation. The blood carries most viruses, as free virions or in the form of infected monocytes, to the target organs, the liver, muscle, joints, and remote lymphoid organs. In these tissues, infection is associated with a marked infiltration of mononuclear cells, including macrophages, particularly when viral replication occurs. The pathological events associated with tissue infection are mostly subclinical in the liver (hepatocyte apoptosis) and lymphoid organs (adenopathy), whereas mononuclear cell infiltration and viral replication in the muscles and joints are associated with very strong pain, with some of the patients presenting arthritis. * Guillain-Barré syndrome and encephalitis are very rare events. † True arthritis remains a rare event (from 2% to 10%); see Table 2.