Studies of Reservoir Hosts for Marburg Virus

Swanepoel, Robert; Smit, Sheilagh B.; Rollin, Pierre E.; Formenty, Pierre; Leman, Patricia A.; Kemp, Alan C.; Burt, Felicity J.; Grobbelaar, Antoinette A.; Croft, Janice E; Bausch, Daniel G.; Zeller, H.; Leirs, Herwig; Braack, L.E.O.; Libande, Modeste L.; Zaki, Sherif R.; Nichol, Stuart T.; Ksiazek, Thomas G.; Pawęska, Janusz T.

doi:10.3201/eid1312.071115

Cited by 260 publications

(241 citation statements)

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“…These data also support earlier findings demonstrating the replication and circulation of ZEBOV in experimentally infected fruit and insectivorous bats in the absence of illness (7). Nonetheless, the higher titers shown in the experimental bat model raise questions as to why virus isolation has not been achieved from any of the naturally infected bat species (20)(21)(22). One suggestion is that virus titers may be very low in these naturally infected animals; consistent with the need for nested RT-PCR to detect ZEBOV-specific nucleic acid, and that specific physiologic or environmental stimuli are needed to stimulate virus production (20).…”

Section: Discussionsupporting

confidence: 78%

“…Because bat species have long been suspected reservoirs for filoviruses and have been recently shown to harbor viral RNA and/or virus-specific antibodies (20)(21)(22), we evaluated a bat cell line for this capability. Similar to RAW264.7, Tbl.Lu cells established ZEBOV persistence and showed little virus propagation, but could be induced to more productive viral infection after PMA treatment (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…What remains unclear is the mechanisms underlying the high susceptibility of some species (i.e., humans and NHPs) to wild-type virus compared with other species (i.e., mice and possibly bats). Recent work has provided support for a role of fruit bats as a reservoir species for EBOV and Marburg virus (20)(21)(22), but whether other species also are involved is not known, and the mechanism of the spillover from reservoir to humans and NHPs remains unclear.…”

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confidence: 99%

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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: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…En un estudio realizado en 1996 una amplia gama de hospedadores fueron infectados experimentalmente con el virus del Ébola. Entre ellos, los murciélagos destacaron porque fueron infectados, replicaron el virus, y sobrevivieron a la infección 9 . En 2005 Leroy et al lograron detectar anticuerpos contra el virus del Ébola y ARN de Ébola en tres especies de murciélagos de la fruta: Hypsignathus monstrosus (24%, 4/17), Epomops franqueti (7%, 8/117) y Myonycteris torquata (7%, 4/58).…”

Section: Reservorio Y Transmisiónunclassified

¿Qué deber saber un médico sobre el ébola?

Riva¹,

García²

2014

Gal. Clin.

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IntroducciónEl reciente brote provocado por el virus Ébola en varios países del oeste africano (Guinea, Liberia, Sierra Leona y Nigeria), se ha traducido, según el último informe de la Organización mundial de la Salud (OMS), en 13.567 infectados y 4.951 fallecidos, cifra que se cree, está subestimada debido a los inexistentes sistemas de sanitarios disponibles en los países centro de la epidemia. Con una mortalidad cercana al 40% ha supuesto una gran preocupación para todos servicios de salud pública mundiales, especialmente, una vez que se ha tenido conocimiento de los primeros casos en los países desarrollados.El virus Ébola fue aislado por primera vez en 1976 y debe su nombre al río que pasaba cerca del país donde se localizó el primer brote, la actual República Democrática del Congo, desde entonces se han contabilizado más de 20 brotes. El actual ha estado afectando a África desde, aproximadamente, diciembre de 2013 teniendo constancia de los primeros casos en el sur de Guinea-Conakry aunque no se identificó hasta el mes de marzo de 2014 1 , lo que ha facilitado la transmisión del virus por la mejora de las comunicaciones entre los países centro de la epidemia 2 . Esta cepa de virus Ébola está fuertemente relacionada con la que está en circulación en África Central desde hace más de 10 años 3 .La OMS declaró la epidemia de Ébola en África occidental una Emergencia en Salud Pública Internacional el 8 de agosto de 2014 4 . El virusEl agente causal de la enfermedad por virus ébola (EVE) es un virus RNA de la familia Filoviridiae y tres grupos Ebolavirus, Marburg y la cepa recientemente descrita por A. Negredo et al del Instituto Carlos III de Madrid los Cuevavirus. Seis cepas diferentes de Ebolavirus han sido identificadas; ebolavirus Zaire (EBOV), ebolavirus Sudán (SUDV), ebolavirus Tai Forest (TAFV), ebolavirus Bundibugyo (BDBV) y ebolavirus Reston (RESTV) 5 . La gran mayoría de los últimos brotes de Ébola en seres humanos han sido vinculados a tres cepas de Ébola: EBOV, SUDV y BDBV 6 .El virus del Ébola, EBOV, es la cepa más mortal de las cinco cepas de virus Ébola y corresponde a la que está actualmente en circulación.Los Filoviridiae tienen forma filamentosa, una envuelta lipídica y contiene un RNA de sentido negativo. El genoma viral codifica una nucleoproteína (NP), la glucoproteína (GP), la ARN polimerasa dependiente de ARN (L), y cuatro proteínas estructurales denominados VP24, VP30, VP35 y VP40. Además, el virus Ébola es capaz de expresar una forma soluble de sGP a través del ARN (Figura 1) 7 . Representa un agente infeccioso, no un ser vivo y el recuerdo de un modelo de conservación de la información genética muy anterior a nuestro propio origen y lo que le ha permitido llegar a producir el daño que ahora nos causa, es su capacidad de adaptación.El virus Ébola posee una envuelta lipídica bicapa que sirve como protección al genoma, facilita la entrada en las células hospedadoras y le permite protegerse de la respuesta inmunitaria del organismo 8 . Reservorio y transmisiónDe las aproximadamente 4.600 e...

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“…Infections with MARV have been linked to human entry into caves inhabited by Egyptian fruit bats (Rousettusaegyptiacus). 2,3 After its first appearance in 1967, several sporadic outbreaks of Marburg hemorrhagic were reported across subSaharan Africa. 1 To date, there have been 2 big outbreaks of Marburg hemorrhagic fever, the 1998-2000 outbreak in the Democratic Republic of the Congo and the 2004-2005 outbreak in Angola.…”

Section: Introductionmentioning

confidence: 99%

A bioluminescent imaging mouse model for Marburg virus based on a pseudovirus system

Zhang

Liu

et al. 2017

Human Vaccines & Immunotherapeutics

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Marburg virus (MARV) can cause lethal hemorrhagic fever in humans. Handling of MARV is restricted to high-containment biosafety level 4 (BSL-4) facilities, which greatly impedes research into this virus. In this study, a high titer of MARV pseudovirus was generated through optimization of the HIV backbone vectors, the ratio of backbone vector to MARV glycoprotein expression vector, and the transfection reagents. An in vitro neutralization assay and an in vivo bioluminescent imaging mouse model for MARV were developed based on the pseudovirus. Protective serum against MARV was successfully induced in guinea pigs, which showed high neutralization activity in vitro and could also protect Balb/c mice from MARV pseudovirus infection in vivo. This system could be a convenient tool to enable the evaluation of vaccines and therapeutic drugs against MARV in non-BSL-4 laboratories.

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Studies of Reservoir Hosts for Marburg Virus

Abstract: Marburg virus nucleic acid was found in 12 bats, antibodies were found in 2 species of these bats, but no live virus was isolated.

Cited by 260 publications

References 13 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

¿Qué deber saber un médico sobre el ébola?

A bioluminescent imaging mouse model for Marburg virus based on a pseudovirus system

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