Dataset Information

The Makona Variant of Ebola Virus Is Highly Lethal to Immunocompromised Mice and Immunocompetent Ferrets.

ABSTRACT: During 2013-2016, a novel isolate of Ebola virus (EBOV-Makona) caused an epidemic in West Africa. The virus was distinct from known EBOV strains (EBOV-Kikwit and EBOV-Mayinga), which were responsible for previous outbreaks in Central Africa. To investigate the pathogenicity of EBOV-Makona, we engineered and rescued an early isolate (H.sapiens-wt/GIN/2014/Makona-Gueckedou-C07, called rgEBOV-C07) using an updated reverse-genetics system. rgEBOV-C07 was found to be highly pathogenic in both the knockout mouse and ferret models, with median lethal dose values of 0.078 and 0.015 plaque-forming units, respectively. Therefore, these animals are appropriate for screening potential countermeasures against EBOV-Makona without the need for species adaptation.

SUBMITTER: Wong G

PROVIDER: S-EPMC6249576 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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The Makona Variant of Ebola Virus Is Highly Lethal to Immunocompromised Mice and Immunocompetent Ferrets.

Wong Gary G Leung Anders A He Shihua S Cao Wenguang W De La Vega Marc-Antoine MA Griffin Bryan D BD Soule Geoff G Kobinger Gary P GP Kobasa Darwyn D Qiu Xiangguo X

The Journal of infectious diseases 20181101 suppl_5

During 2013-2016, a novel isolate of Ebola virus (EBOV-Makona) caused an epidemic in West Africa. The virus was distinct from known EBOV strains (EBOV-Kikwit and EBOV-Mayinga), which were responsible for previous outbreaks in Central Africa. To investigate the pathogenicity of EBOV-Makona, we engineered and rescued an early isolate (H.sapiens-wt/GIN/2014/Makona-Gueckedou-C07, called rgEBOV-C07) using an updated reverse-genetics system. rgEBOV-C07 was found to be highly pathogenic in both the kno ...[more]

PMID: 29878131

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Project description:Ebola virus (EBOV) has been responsible for sporadic outbreaks in Central Africa since 1976 and has the potential of causing social disruption and public panic as illustrated by the 2013-2016 epidemic in West Africa. Transmission of EBOV has been described to occur via contact with infected bodily fluids, supported by data indicating that infectious EBOV could be cultured from blood, semen, saliva, urine, and breast milk. Parameters influencing transmission of EBOV are, however, largely undefined in part due to the lack of an established animal model to study mechanisms of pathogen spread. Here, we investigated EBOV transmissibility in male and female ferrets. After intranasal challenge, an infected animal was placed in direct contact with a naive ferret and in contact with another naive ferret (separated from the infected animal by a metal mesh) that served as the indirect-contact animal. All challenged animals, male direct contacts, and one male indirect contact developed disease and died. The remaining animals were not viremic and remained asymptomatic but developed EBOV-glycoprotein IgM and/or IgG specific antibodies-indicative of virus transmission. EBOV transmission via indirect contact was frequently observed in this model but resulted in less-severe disease compared to direct contact. Interestingly, these observations are consistent with the detection of specific antibodies in humans living in areas of EBOV endemicity.IMPORTANCE Our knowledge regarding transmission of EBOV between individuals is vague and is mostly limited to spreading via direct contact with infectious bodily fluids. Studying transmission parameters such as dose and route of infection is nearly impossible in naturally acquired cases-hence the requirement for a laboratory animal model. Here, we show as a proof of concept that ferrets can be used to study EBOV transmission. We also show that transmission in the absence of direct contact is frequent, as all animals with indirect contact with the infected ferrets had detectable antibodies to the virus, and one succumbed to infection. Our report provides a new small-animal model for studying EBOV transmission that does not require adaptation of the virus, providing insight into virus transmission among humans during epidemics.

Dataset Information

The Makona Variant of Ebola Virus Is Highly Lethal to Immunocompromised Mice and Immunocompetent Ferrets.

Publications

The Makona Variant of Ebola Virus Is Highly Lethal to Immunocompromised Mice and Immunocompetent Ferrets.

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