Pathogenesis of filoviral haemorrhagic fevers.
The filoviruses, marburgvirus and ebolavirus, cause epidemics of haemorrhagic fever with high case-fatality rates. The severe illness results from a complex of pathogenetic mechanisms that enable the virus to suppress innate and adaptive immune responses, infect and kill a broad variety of cell types, and elicit strong inflammatory responses and disseminated intravascular coagulation, producing a syndrome resembling septic shock. Most experimental data have been obtained on Zaire ebolavirus, which causes uniformly lethal disease in experimentally infected non-human primates but produces a broader range of outcomes in naturally infected human beings. 10-30% of patients can survive the illness by mobilising adaptive immune responses, and there is limited evidence that mild or symptomless infections also occur. The other filoviruses that have caused human disease, Sudan ebolavirus, Ivory Coast ebolavirus, and marburgvirus, produce a similar illness but with somewhat lower case-fatality rates. Variations in outcome during an epidemic might be due partly to genetically determined differences in innate immune responses to the viruses. Recent studies in non-human primates have shown that blocking of certain host responses, such as the coagulation cascade, can result in reduced viral replication and improved host survival.
Malaria Vaccine Development Unit, at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Siddhartha
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Mahanty
Mike
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Bray
D000349:Africa / Q000453:epidemiology; D000818:Animals; D004197:Disease Reservoirs; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008379:Marburg Virus Disease / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D029024:Marburgvirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity