Interestingly, infected animals were able to mount an immune response that was in many ways similar to the responses observed during Ebola contamination in nonhuman primates

Interestingly, infected animals were able to mount an immune response that was in many ways similar to the responses observed during Ebola contamination in nonhuman primates. in the Ebola River valley in Zaire (now the Democratic Republic of the Congo), Africa. A second outbreak caused by a unique but related computer virus occurred in Sudan later the same 12 months1,2. Since its discovery in central Africa, several outbreaks have recurred over the last 30 years, including a current confirmed outbreak (11 September 2007) in the Democratic Republic of the Congo ( Even though reservoir of computer virus in nature and the range of intermediate hosts is not fully understood, recent studies have found that fruit bats may support replication of Ebola computer virus, indicating that these animals may be involved in the life cycle of the computer virus3. However, the natural host of Ebola computer virus in the absence of active outbreaks, together with the important question of how it is transmitted among numerous species, represents a continuing subject of investigation. Human infections usually occur after direct contact with computer virus in lifeless or infected people or wildlife, with subsequent person-to-person transmission. Filoviruses enter the body through mucosal surfaces or skin abrasions or through the use of contaminated needles4 (Fig. 1a). The onset of Ebola virusCinduced disease is usually sudden, with a 4 to 10 day incubation period. Patients in the beginning show nonspecific flu-like symptoms such as fever, chills, malaise, muscle aches and headache. Abdominal pain, nausea and vomiting may follow, and a cough, sore throat or diarrhea may also be present. A rash often appears around day five and is a characteristic feature of filovirus contamination. Systemic, gastrointestinal, respiratory, vascular and neurologic manifestations result from considerable viral replication, and necrosis is seen in many organs, including the liver, spleen, kidneys and gonads5. The terminal stage of the disease is characterized by coagulation disorders such as disseminated intravascular coagulation, fluid distribution problems, hypotension and hemorrhage due to liver inflammation and compromise, tissue disruption and a breakdown in endothelial barrier function that DM1-Sme leads to increased vascular permeability. In fatal cases, death occurs typically between 7 and 16 days after contamination, the result of multiple organ failure and the onset of a syndrome that resembles severe septic shock6. There are currently no antiviral drugs to treat contamination and the mortality rates for the more virulent Zaire and Sudan DM1-Sme species of the computer virus range from 40C90%7. Open in a separate window Physique 1 Infection, spread and target cell destruction by Ebola computer virus.(a) Ebola computer virus (yellow) infects subjects through contact with body fluid or secretions from an infected patient and is distributed through the blood circulation. Entry can occur through abrasions in the skin during patient care, burial rituals and possibly contact with infected bushmeat, or across mucosal surfaces. Accidental needle stick is the main route of occupational exposure. (b) Early targets of replication are reticuloendothelial cells, with high replication in several cell types within the lungs, liver and spleen. (c) Dendritic cells, macrophages and endothelium appear to be susceptible to cytopathic effects of Ebola computer virus gene products and possibly through disruption of cellular signaling pathways affected by computer virus binding, phagocytic uptake or both. Indirect damage may also be inflicted by circulating factors such as tumor necrosis factor and nitric oxide. Rabbit Polyclonal to RHBT2 Host immune response to fatal Ebola contamination The uncontrolled viral replication of Ebola computer virus is usually central to its pathogenesis, both because of its cytopathic effects and because it induces prominent dysregulation of the host DM1-Sme immune response. Virally induced immune system impairment occurs through a variety of mechanisms. Studies in nonhuman primates as well as guinea pigs raise the possibility that monocytes, macrophages and dendritic cells are early and favored sites of viral replication8,9, though it remains possible that DM1-Sme computer virus is present on these cells through binding to lectin receptors rather than active replication show quick activation of triggering receptor expressed on myeloid cells-1 (TREM-1)13; this results in the release of further inflammatory cytokines and chemokines that contribute to vasodilation and increased vascular DM1-Sme permeability. In addition, infected monocytes and macrophages express cell surface tissue factor, which may be involved in the development of coagulopathies14. After productive infection, macrophages undergo cell lysis and apoptosis in large numbers15; thus, activated monocytes and macrophages do not seem to deter viral spread. Rather, they may contribute to dissemination by supporting viral replication or by transporting computer virus bound to cell surface lectin binding proteins within the lymphatic system. And like neutrophils, monocytes and macrophages may also.