File:Fmicb-13-1040093-g001.jpg

English: Pathogenesis of severe viral hemorrhagic fever. (A) Antigen presenting cells (APCs) present an immature phenotype with low expression of co-stimulatory molecules and low type I interferon (IFN-I) production, leading to poor NK and T cells activation causing a generalized immunosuppression, which lead to uncontrolled viral replication and high viral burdens. (B) During the infection monocytes and macrophages produced large quantities of proinflammatory mediators causing the phenomenon known as cytokine storm. These proinflammatory mediators cause endothelial and platelet activation and induce bystander activation and apoptosis of T cells. (C) Infected APC transport Hemorrhagic fever viruses (HFVs) to lymph nodes and other organs causing a systemic dissemination. Infection of some organs such as liver and adrenal gland results in high serum levels of hepatic enzymes (aspartate amino transferase-AST, and alanine amino transferase-ALT), low production of clotting factors and hypovolemia. (D) Sustained proinflammatory state and viral infection of endothelial cells induce abnormal vascular regulation and organ effusion, hemorrhages, and disseminated intravascular coagulation (DIC).