Filovirus - Pathogenesis

Pathogenesis of Filovirus

Initial targets for filovirus replication are monocytes/macrophages and dendritic cells. Infection results in the activation of monocytes/macrophages with the systemic release of cytokines, chemokines, and other mediators such as tissue necrosis factor. Infection of dendritic cells leads to decreased ability to:-

• secrete proinflammatory cytokines, a lack of up-regulation of co-stimulatory molecules

• stimulate T-cells

• produce Type I IFN

* All these results in increased vascular permeability disseminated intravascular coagulation and impaired immune responses

Infected target cells travel to regional lymph nodes, liver, and spleen, where resident macrophages and dendritic cells get infected resulting in the dissemination of the virus. Thus lover and adrenal cortex are secondary target sites where extensive viral replication and host cell necrosis take place.

Liver impairment contributes to overall pathogenesis by exacerbating (to increase severity) coagulation abnormalities (decreased synthesis of coagulation factors and other plasma proteins). Impairment of the adrenal cortex leads to hypotension and Na loss with hypovolemia (decreased blood volume).

Late in Filovirus infection, extensive necrosis of parenchymal cells (fundamental/main cell) of the liver, spleen, kidney, and gonads with little infiltration of immune cells into the infected is observed. Lymphocytes are also destroyed due to infection.

Mediator-induced inflammatory responses from primary target cells (i.e. monocytes/macrophages), severely disrupted coagulation, and fibrinolysis occurs. Fibrin deposition results in the development of microvascular thrombi in various organs leading to ischemia (less blood supply to tissues) and impaired organ perfusion, which contributes to multi-organ failure dysfunction.