Marburg-Virus Disease in Kenya

Smith, Dwayne; Isaäcson, M; Johnson, Karl M.; Bagshawe, A.; Johnson, Bruce K.; Swanapoel, R.; Killey, M.; Siongok, T. A.; Keruga, W. Koinange

doi:10.1016/s0140-6736(82)91871-2

Cited by 274 publications

(213 citation statements)

References 3 publications

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“…Gupta et al (47) were able to establish persistent infection with MA-ZEBOV in immunodeficient mice. The fact that during naturally acquired human infections filoviruses have been isolated from seminal fluid months after disease onset and recovery, also suggests that more prolonged filoviral infections or delay in virus clearance from privileged sites can occur (29,(48)(49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

Strong

Wong²,

Jones³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV ''jumps'' from an infected animal to a person and is subsequently transmitted between persons by direct contact with infected blood or body fluids. This study was undertaken to investigate the mechanism by which EBOV can persistently infect and then escape from model cell and animal reservoir systems. We report a model system in which infection of mouse and bat cell lines with EBOV leads to persistence, which can be broken with low levels of lipopolysaccharide or phorbol-12-myristate-13-acetate (PMA). This reactivation depends on the Ras/MAPK pathway through inhibition of RNA-dependent protein kinase and eukaryotic initiation factor 2␣ phosphorylation and occurs at the level of protein synthesis. EBOV also can be evoked from mice 7 days after infection by PMA treatment, indicating that a similar mechanism occurs in vivo. Our findings suggest that EBOV may persist in nature through subclinical infection of a reservoir species, such as bats, and that appropriate physiological stimulation may result in increased replication and transmission to new hosts. Identification of a presumptive mechanism responsible for EBOV emergence from its reservoir underscores the ''hit-and-run'' nature of the initiation of human and/or nonhuman primate EBOV outbreaks and may provide insight into possible countermeasures to interfere with transmission.

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Section: Discussionmentioning

confidence: 99%

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

Strong

Wong²,

Jones³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Experimental infection conditions consisted of maintenance of 2.5 ϫ 10 6 PBMC and 2.5 ϫ 10 5 HMVEC in segregated cultures. Cells were infected at an m.o.i of 1.0 with EBO-Z virus isolated from a human patient in 1976 (Johnson et al, 1977), EBO-R virus isolated from a nonhuman primate in 1989 (Jahrling et al, 1990), or MBG (strain Musoke) virus isolated from a human patient in 1980 (Smith et al, 1982). PBMC were incubated in the presence of infectious virus for 3 hours at 37°C, washed with RPMI, and replated in fresh medium.…”

Section: Cells and Virusesmentioning

confidence: 99%

Apoptosis Induced In Vitro and In Vivo During Infection by Ebola and Marburg Viruses

Geisbert

Hensley

Gibb

et al. 2000

Laboratory Investigation

289

254

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SUMMARY:Induction of apoptosis has been documented during infection with a number of different viruses. In this study, we used transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling to investigate the effects of Ebola and Marburg viruses on apoptosis of different cell populations during in vitro and in vivo infections. Tissues from 18 filovirus-infected nonhuman primates killed in extremis were evaluated. Apoptotic lymphocytes were seen in all tissues examined. Filoviral replication occurred in cells of the mononuclear phagocyte system and other well-documented cellular targets by TEM and immunohistochemistry, but there was no evidence of replication in lymphocytes. With the exception of intracytoplasmic viral inclusions, filovirus-infected cells were morphologically normal or necrotic, but did not exhibit ultrastructural changes characteristic of apoptosis. In lymph nodes, filoviral antigen was co-localized with apoptotic lymphocytes. Examination of cell populations in lymph nodes showed increased numbers of macrophages and concomitant depletion of CD8 ϩ T cells and plasma cells in filovirus-infected animals. This depletion was particularly striking in animals infected with the Zaire subtype of Ebola virus. In addition, apoptosis was demonstrated in vitro in lymphocytes of filovirus-infected human peripheral blood mononuclear cells by TEM. These findings suggest that lymphopenia and lymphoid depletion associated with filoviral infections result from lymphocyte apoptosis induced by a number of factors that may include release of various chemical mediators from filovirus-infected or activated cells, damage to the fibroblastic reticular cell conduit system, and possibly stimulation by a viral protein. (Lab Invest 2000, 80:171-186).I nfections with filoviruses cause severe and often fatal hemorrhagic disease in humans and nonhuman primates, killing up to 90% of infected individuals. Ebola (EBO) and Marburg (MBG) viruses comprise the family Filoviridae (Murphy et al, 1995). The EBO species consists of the Zaire and Sudan subtypes first isolated during separate outbreaks in 1976, the Reston subtype initially isolated from monkeys imported from the Philippines to the United States in 1989, and the Cô te d'Ivoire subtype discovered in the Tai Forest of the Ivory Coast in 1994. The recent re-emergence of EBO subtype Zaire (EBO-Z) in former Zaire and Gabon, and subtype Reston (EBO-R) in the United States, are but the last of a succession of filoviral outbreaks that have occurred sporadically since the initial zoonotic outbreak of MBG in 1967. Although outbreaks have been self-limiting, the lack of proven effective prophylactic or therapeutic regimens to treat filoviral infections has heightened concerns about the public health threat of these pathogens.The factors contributing to the development of severe lesions in EBO and MBG hemorrhagic fevers are unknown. Filoviral infections of humans and nonhuman primates are characterized by a failure o...

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“…The first outbreak of MARV occurred in 1967 in Marburg, Germany, following exposure to monkeys imported from Uganda. This was followed almost 10 years later in 1976 by the first recognized outbreak of EBOV in the country Democratic Republic of the Congo, formerly known as Zaire [3][4][5]. The natural hosts of EBOV and MARV are unknown, although human cases occur most often due to contact with infected monkeys, humans, or their blood and tissues [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…This was followed almost 10 years later in 1976 by the first recognized outbreak of EBOV in the country Democratic Republic of the Congo, formerly known as Zaire [3][4][5]. The natural hosts of EBOV and MARV are unknown, although human cases occur most often due to contact with infected monkeys, humans, or their blood and tissues [4][5][6]. Natural outbreaks have been on the rise recently, most likely not only due in part to improved surveillance, but also due to more frequent contact between monkeys and humans because of the destruction of natural habitats in Africa (http://www.who.int/disease-outbreaknews/disease/bydisease.htm).…”

Section: Introductionmentioning

confidence: 99%

Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections

Swenson

Warfield

Negley

et al. 2005

Vaccine

123

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Marburg-Virus Disease in Kenya

Cited by 274 publications

References 3 publications

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

Apoptosis Induced In Vitro and In Vivo During Infection by Ebola and Marburg Viruses

Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections

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