Ebola pathophysiology On the Web
American Roentgen Ray Society Images of Ebola pathophysiology
The Ebola virus infects the mononuclear phagocyte system, but also other cells such as hepatocytes, spongiocytes, fibroblasts and endothelial cells, inducing tissue necrosis and disrupting the hematological and coagulation systems. The Ebola virus is transmitted by direct contact with infected patients or animals. The natural reservoir has not been identified.
- Ebola virus infects mainly the cells of the mononuclear phagocyte system, but also fibroblasts, hepatocytes, spongiocytes, adrenal cortical cells and endothelial cells.
- The infection of the mononuclear phagocyte system cells plays a key role in the pathogenesis and spread of the disease as they carry the virus from of the initial infection site, through the lymphatic system and blood, to the regional lymph nodes,spleen and liver.
- The next table summarizes the pathogenesis of the disease according to the virus tropism.
|Endothelial cells||Glycoprotein (GP) on the virion envelope allows introduction of its content into the endothelial cells, which induces a cytopathic effect and damage to the endothelial barrier function that, together with effects of TNF-α released by infected mononuclear cells, leads to the loss of vascular integrity and increased leakage.|
|Liver||Causes hepatocellular necrosis which could impair the synthesis of proteins of the coagulation system|
|Adrenal cortex||Affects the synthesis of enzymes responsible for the synthesis of steroids, leading to hypotension, and fluid and electrolytes disturbances.|
|Lymphatic system||Necrosis of the spleen, lymph nodes and thymus; Apoptosis of lymphocytes leading to lymphopenia.|
- The virus activates the macrophages synthesis of interleukins (IL), which leads the Th1/Th2 balance towards a more pronounced Th1-cell mediated response.
- Some inflammatory mediators produced during the ebola virus infection include: interferon (IFN)-alpha, IFN-beta, IL-2, IL-6, IL-8, IL-10, interferon-inducible protein 10; monocyte chemoattractant protein 1; regulated upon activation normal T cell expressed and secreted (RANTES); TNF-alpha; and reactive oxygen and nitrogen species.
- Some viral proteins, such as VP35 and VP24, block the type I interferon response, which plays a key role of the pathogenesis of the disease.
- The reactive oxygen and nitrogen species contribute to the cell and tissue damage, and therefore vascular and organ damage.
- The nitric oxide is known to be an important vasodilator, therefore it plays and important role in the development of hypotension and shock.
- Ebola infection is associated with hemorrhage in 50% of patients.
- Alterations of the coagulation system are induced by the ebola virus, and are thought to be mediated by the production of tissue factor:
Understanding the immune response to the disease
In one case study performed on an individual who had severe Ebola virus infection in Sierra Leone to further understand the immune response during all the stages of the disease. The individual was provided with supportive care only without any other experimental therapies. Daily global gene expression in peripheral white blood cells was recorded and correlated with many clinical and laboratory aspects during the course of disease (Viral load, multiple organ dysfunction, coagulopathy, etc) till complete recovery after 33 days.
The study enabled us to identify the host responses (the genomic shift between increased expression of genes involved in inflammation and cell destruction to increased expression of genes promoting cell repair) that correlate with the viral clearance and recovery.
The study revealed that many changes in gene expression precede the change in the clinical status of the patient emphasizing the role of viral clearance in the cure of systemic illness.
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