Chapter 42 : Filoviruses

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The filoviruses are nonsegmented, negative-sense RNA viruses in the family , order . The genus consists of a single species of related viruses, for which bats in Central Africa have recently been found to be a reservoir. The other genus, , contains four species (Zaire, Sudan, Bundibugyo, and Ivory Coast) indigenous to Africa, and a fifth, Reston virus, found in the Philippines. It is likely that the African Ebola species are also maintained in bats, but attempts to recover infectious virus from captured animals have been unsuccessful. Except for the Reston agent, all filoviruses cause severe disease in humans, with fatality rates in outbreaks often exceeding 50%.

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 1

A. Negative-contrast electron micrograph (EM) of Ebola virions (magnification, ×17,000). B. Transmission EM of viral nucleocapsids in a cytoplasmic inclusion body. C. Scanning EM of virions budding from the surface of an infected cell. (Courtesy of Tom Geisbert, USAMRIID.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 2

Outbreaks of Marburg and Ebola virus disease in Africa, 1976–2014. All Marburg outbreaks have been caused by a single virus species. Most Ebola epidemics have been caused by the Zaire species (EBOV), with the Sudan virus (SUDV) responsible for a smaller number in East Africa. The Bundibugyo (BDBV) virus has been identified only in Uganda and the Ivory Coast virus in a single human infection in the Tai Forest in that country (TAFV). (Courtesy of Eric Leroy, CIRMF, Gabon. Reprinted with permission from Reference .)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 3

The iconic figure of the West African Ebola epidemic: a health care worker in full personal protective equipment (PPE). The outbreak began in a rural village in Guinea in late 2013, then spread to the largest cities of Guinea, Sierra Leone, and Liberia. By January, 2016, more than 28,000 suspected, probable, and confirmed cases had been reported—more than 10 times the total of all previous Ebola epidemics combined—and 11,000 deaths ( ) (Photo provided by Médecins Sans Frontières, used with permission.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 4

Bayesian coalescent analysis of genomic sequences of the , based on representative viruses chosen from each species and a diverse set of isolates. Values at each node represent years since most recent common ancestor, prior to 2007. The tree indicates the early divergence of the genera , , and . Although the Marburg Ravn and Musoke viruses have followed a separate evolutionary course for approximately 1,000 years, they are still more closely related to each other than any two species in the genus . The Sudan and Reston viruses are the most distantly related to other Ebola viruses. (Reprinted from Reference with permission.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 5

A. Structure of a filovirus virion, showing the RNA genome with its associated nucleocapsid proteins, enveloped in a lipid bilayer bearing glycoprotein spikes. NP and VP30 bind to virion RNA to make up the nucleocapsid, and VP35 and the RNA polymerase (L protein) join them in forming a replication complex. Matrix proteins VP24 and VP40 link the nucleocapsid to GP on the inner surface of the envelope. B. Schematic representation of the genomes of Marburg and Ebola viruses. The seven genes are drawn roughly to scale. (Courtesy of Eric Leroy, CIRMF, Gabon. Reprinted from Reference with permission.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 6

The West African Ebola epidemic: patient care in a low-resource setting. A. Medical workers preparing to enter an Ebola treatment unit. A team approach ensures that PPE is donned and removed correctly. B. ELWA-3, the largest Ebola treatment center ever constructed, built by Médecins Sans Frontières adjacent to the ELWA mission hospital in Monrovia, Liberia. The center is designed to isolate persons possibly incubating Ebola virus disease, treat those who have become ill, and prevent the further spread of infection. (Médecins Sans Frontières, used with permission.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 8

Pathogenesis of filovirus disease. Monocytes, macrophages, and dendritic cells are the primary sites of replication. Suppression of type I interferon responses permits rapid virus dissemination via the bloodstream to the spleen and other lymphoid tissues and to hepatocytes and parenchymal cells of other organs, resulting in further productive infection and multifocal necrosis. The release of proinflammatory mediators, the production of cell-surface tissue factor, and endothelial dysfunction contribute to coagulopathy, organ-specific vascular leak (e.g. lungs), and eventual multi-organ failure. Lymphocytes remain uninfected but undergo apoptosis, contributing to the failure of adaptive immune responses. Note: observations in patients during the West African Ebola outbreak suggest that damage to renal parenchymal cells and injury within the central nervous system plays a significant role in pathogenesis.

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 9

Replication of mouse-adapted Ebola virus in a lethally infected mouse. A. hybridization of viral RNA in a splenic follicle; all marginal-zone macrophages contain replicating virus, while lymphocytes remain uninfected. B. Multifocal necrosis in the liver. Some hepatocytes contain acidophilic inclusion bodies (arrow), corresponding to the nucleocapsid aggregates shown in Figure 2B . (Courtesy of Tammy Gibb and Kelly Davis, USAMRIID.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 10

Extensive desquamation of the forearm and hand of a survivor of Ebola Sudan virus infection in Gulu, Uganda, 3 weeks after disease onset. (Courtesy of Dan Bausch, Tulane University.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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Image of FIGURE 7

The West African Ebola epidemic: patient care in a high-resource setting. Coauthor DC manipulating a peripherally inserted central catheter line of a critically ill Ebola patient requiring mechanical ventilation in the Special Clinical Studies Unit of the Clinical Center, National Institutes of Health, Bethesda, MD.

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
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