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Unformatted text preview: J OURNAL OF VIROLOGY, Sept. 2003, p. 97339737 Vol. 77, No. 18 0022-538X/03/$08.00 1 0 DOI: 10.1128/JVI.77.18.97339737.2003 MINIREVIEW Ebola Virus Pathogenesis: Implications for Vaccines and Therapies Nancy Sullivan, Zhi-Yong Yang, and Gary J. Nabel* Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Ebola virus is an aggressive pathogen that causes a highly lethal hemorrhagic fever syndrome in humans and nonhuman primates. First recognized near the Ebola River valley during an outbreak in Zaire in 1976 (6, 20), outbreaks have occurred in Africa in the ensuing 27 years, with mortality rates ranging from 50 to 90% (26, 28). Outbreaks have been identified yearly for the past 3 years in central Africa, the most recent of which continues in the Republic of the Congo, with more than 125 fatalities to date according to the World Health Organization (http://www.who.int/csr/don/2003 o 05 o 07/en/, accessed 7 May 2003). The natural host for Ebola virus is unknown, so it has not been possible to implement programs to control or elimi- nate viral reservoirs of transmission to human populations. The rapid progression of Ebola virus infection has further complicated the control of this disease, affording little oppor- tunity to develop acquired immunity. There is currently no antiviral therapy or vaccine that is effective against Ebola virus infection in humans. Although its clinical course is well known, the specific mech- anisms underlying the pathogenicity of Ebola virus have not been clearly delineated. This is due, in part, to the difficulty in obtaining samples and studying the disease in the relatively remote areas in which the outbreaks occur. In addition, a high degree of biohazard containment is required for laboratory studies and clinical analysis. Isolation of the viral cDNAs and the development of expression systems have allowed the study of Ebola virus gene products under less restrictive conditions and facilitated an understanding of the mechanisms underlying virally induced cell damage. EBOLA VIRUS DISEASE PROGRESSION Typically, Ebola virus infection runs its course within 14 to 21 days. Infection initially presents with nonspecific flu-like symptoms such as fever, myalgia, and malaise. As the infection progresses, patients exhibit severe bleeding and coagulation abnormalities, including gastrointestinal bleeding, rash, and a range of hematological irregularities, such as lymphopenia and neutrophilia. Cytokines are released when reticuloendothelial cells encounter virus, which can contribute to exaggerated in- flammatory responses that are not protective. Damage to the liver, combined with massive viremia, leads to disseminated intravascular coagulopathy. The virus eventually infects micro- vascular endothelial cells and compromises vascular integrity....
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