<unk>  virus is passed to humans when a bite from an infected mosquito breaks the skin and introduces the virus into the body. The pathogenesis of<unk>  infection in humans is still poorly understood, despite recent outbreaks. It appears that in vitro,<unk>  virus is able to replicate in human epithelial and endothelial cells, primary fibroblasts, and monocyte-derived macrophages. Viral replication is highly cytopathic, but susceptible to type-I and -II interferon. In vivo, in studies using living cells,<unk>  virus appears to replicate in fibroblasts, skeletal muscle progenitor cells, and myofibers. The type-1 interferon response seems to play an important role in the host's response to<unk>  infection. Upon infection with<unk> , the host's fibroblasts produce type-1 alpha and beta interferon (IFN-α and IFN-β). In mouse studies, deficiencies in INF-1 in mice exposed to the virus cause increased morbidity and mortality. The<unk> -specific upstream components of the type-1 interferon pathway involved in the host's response to<unk>  infection are still unknown. Nonetheless, mouse studies suggest that IPS-1 is an important factor, and that IRF3 and IRF7 are important in an age-dependent manner. Mouse studies also suggest that<unk>  evades host defenses and counters the type-I interferon response by producing NS2, a nonstructural protein that degrades RBP1 and turns off the host cell's ability to transcribe DNA. NS2 interferes with the JAK-STAT signaling pathway and prevents STAT from becoming phosphorylated. In the acute phase of<unk> , the virus is typically present in the areas where symptoms present, specifically skeletal muscles, and joints. In the chronic phase, it is suggested that viral persistence (the inability of the body to entirely rid itself of the virus), lack of clearance of the antigen, or both, contribute to joint pain. The inflammation response during both the acute and chronic phase of the disease results in part from interactions between the virus and monocytes and macrophages.<unk>  virus disease in humans is associated with elevated serum levels of specific cytokines and chemokines. High levels of specific cytokines have been linked to more severe acute disease: interleukin-6 (IL-6), IL-1β, RANTES, monocyte chemoattractant protein 1 (MCP-1), monokine induced by gamma interferon (MIG), and interferon gamma-induced protein 10 (IP-10). Cytokines may also contribute to chronic<unk>  virus disease, as persistent joint pain has been associated with elevated levels of IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In those with chronic symptoms, a mild elevation of C-reactive protein (CRP) has been observed, suggesting ongoing chronic inflammation. However, there is little evidence linking chronic<unk>  virus disease and the development of autoimmunity. Viral replication Transmission electron micrograph of<unk>  virus particles The virus consists of four nonstructural proteins and three structural proteins. The structural proteins are the capsid and two envelope glycoproteins: E1 and E2, which form heterodimeric spikes on the viron surface. E2 binds to cellular receptors in order to enter the host cell through receptor-mediated endocytosis. E1 contains a fusion peptide which, when exposed to the acidity of the endosome in eukaryotic cells, dissociates from E2 and initiates membrane fusion that allows the release of nucleocapsids into the host cytoplasm, promoting infection. The mature virion contains 240 heterodimeric spikes of E2/E1, which after release, bud on the surface of the infected cell, where they are released by exocytosis to infect other cells.
Chikungunya
Zika fever
Yellow fever
Dengue fever
Trench fever
Rocky Mountain spotted fever
Cuban fever
Blackwater fever