Pathogenesis of Crimean–Congo Hemorrhagic Fever From an Immunological Perspective

Abstract

Crimean–Congo hemorrhagic fever (CCHF) is a severe viral infection disease. Infection is a battle between the virus and host immune system. The CCHF virus can enter to the organism by way of skin, mucosa, or inhalation and encounters innate immune system cells like monocytes, macrophages, and dendritic cells. These cells cannot successfully eliminate viruses. Thus, the viruses are able to disseminate to regional lymph nodes and to whole body. Different viral pathogen-associated molecular patterns (PAMPs) stimulate the intracellular Toll-like receptors, RIG-like Helicase receptors, and NOD-like receptors. So, different inflammatory cytokines, chemokines, and adhesion molecules are induced. The virus has both direct cytopathic effects on parenchymal cells especially on the liver, spleen, and endothelial cells and non-cytopathic indirect effects depending upon releasing factors from innate immune cells. In severe fatal cases, infection causes coagulation by stimulating both intrinsic and extrinsic coagulation pathways and disseminated intravascular coagulopathy occurs. The prognosis of the disease is dependent on the balance between the viral load and host’s immune system. While high values of IL-12/IL-10, IL-15/IL-10, IL-18/IL-10, and IFN-γ/IL-10 ratios show strong TH1 immune status, low values show suppressed immune system. These ratios together with viral load can indicate the patients’ clinical prognosis from an immunological perspective.