The evolution of Ebola virus: Insights from the 2013–2016 epidemic

Holmes, Edward C.; Dudas, Gytis; Rambaut, Andrew; Andersen, Kristian G.

doi:10.1038/nature19790

Cited by 277 publications

(259 citation statements)

References 94 publications

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“…From a disease prevention point of view, screening and detection of Human papillomavirus infection provides protection against the development of invasive cervical cancer (Ronco et al, 2014), detection of Heliocobacter pylori is indicative of risk for peptic ulcers (Chan et al, 2002), and hospital outbreak as well as epidemic investigations via pathogen sequencing can identify the initial source of an infection and prevent its transmission (Holmes et al, 2016; Lefterova et al, 2015). Pathogen sequencing is also being increasingly utilized in environmental monitoring applications, for example by monitoring influenza reservoirs in animal populations, identifying novel viral antigens, and ultimately informing the development of seasonal vaccines (Ampofo et al, 2015).…”

Section: High Definition Preventionmentioning

confidence: 99%

High-Definition Medicine

Torkamani

Andersen

Steinhubl

et al. 2017

Cell

Self Cite

186

139

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The foundation for a new era of data-driven medicine has been set by recent technological advances that enable the assessment and management of human health at an unprecedented level of resolution – what we refer to as high definition medicine. Our ability to assess human health in high definition is enabled, in part, by advances in DNA sequencing, physiological and environmental monitoring, advanced imaging and behavioral tracking. Our ability to understand and act upon these observations at equally high precision is driven by advances in genome editing, cellular reprogramming, tissue engineering, and information technologies, especially artificial intelligence. In this review, we will examine the core disciplines that enable high definition medicine, and project how these technologies will alter the future of medicine.

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Section: High Definition Preventionmentioning

confidence: 99%

High-Definition Medicine

Torkamani

Andersen

Steinhubl

et al. 2017

Cell

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186

139

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“…It has been suggested that recent ZIKV epidemics may be linked causally to a higher apparent evolutionary rate for the Asian genotype than the African genotype 25,26 . However, such comparisons are confounded by an inverse relationship between the timescale of observation and estimated evolutionary rates 27 .…”

mentioning

confidence: 99%

Establishment and cryptic transmission of Zika virus in Brazil and the Americas

Faria

Quick

Claro

et al. 2017

Nature

528

485

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Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil1. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 20162) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 20162). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease3. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

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“…Moreover, the approaches that are farthest advanced in the pipeline exclusively target the Zaire ebolavirus. Despite this focus, EBOV accounted for only 58% of EVD cases prior to the 2014 outbreak (20). Thus, the benefit of broader therapeutic approaches is clear.…”

Section: Discussionmentioning

confidence: 99%

Novel Cross-Reactive Monoclonal Antibodies against Ebolavirus Glycoproteins Show Protection in a Murine Challenge Model

Duehr

Wohlbold

Oestereich

et al. 2017

J Virol

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Out of an estimated 31,100 cases since their discovery in 1976, ebolaviruses have caused approximately 13,000 deaths. The vast majority (ϳ11,000) of these occurred during the 2013-2016 West African epidemic. Three out of five species in the genus are known to cause Ebola Virus Disease in humans. Several monoclonal antibodies against the ebolavirus glycoprotein are currently in development as therapeutics. However, there is still a paucity of monoclonal antibodies that can cross-react between the glycoproteins of different ebolavirus species, and the mechanism of these monoclonal antibody therapeutics is still not understood in detail. Here, we generated a panel of eight murine monoclonal antibodies (MAbs) utilizing a prime-boost vaccination regimen with a Zaire ebolavirus glycoprotein expression plasmid followed by infection with a vesicular stomatitis virus expressing the Zaire ebolavirus glycoprotein. We tested the binding breadth of the resulting monoclonal antibodies using a set of recombinant surface glycoproteins from Reston, Taï Forest, Bundibugyo, Zaire, Sudan, and Marburg viruses and found two antibodies that showed pan-ebolavirus binding. An in vivo Stat2 Ϫ/Ϫ mouse model was utilized to test the ability of these MAbs to protect from infection with a vesicular stomatitis virus expressing the Zaire ebolavirus glycoprotein. Several of our antibodies, including the broadly binding ones, protected mice from mortality despite lacking neutralization capability in vitro, suggesting their protection may be mediated by Fc-FcR interactions. Indeed, three antibodies displayed cellular phagocytosis and/or antibody-dependent cell-mediated cytotoxicity in vitro. Our antibodies, specifically the two identified cross-reactive monoclonal antibodies (KL-2E5 and KL-2H7), might add to the understanding of anti-ebolavirus humoral immunity.IMPORTANCE This study describes the generation of a panel of novel anti-ebolavirus glycoprotein monoclonal antibodies, including two antibodies with broad crossreactivity to all known ebolavirus species. The antibodies were raised using a heterologous DNA-viral vector prime-boost regimen, resulting in a high proportion of cross-reactive antibodies (25%). Similar vaccination regimens have been used successfully to induce broad protection against influenza viruses in humans, and our limited data indicate that this might be a useful strategy for filovirus vaccines as well. Several of our antibodies showed protective efficacy when tested in a novel murine challenge model and may be developed into future therapeutics.

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The evolution of Ebola virus: Insights from the 2013–2016 epidemic

Cited by 277 publications

References 94 publications

High-Definition Medicine

High-Definition Medicine

Establishment and cryptic transmission of Zika virus in Brazil and the Americas

Novel Cross-Reactive Monoclonal Antibodies against Ebolavirus Glycoproteins Show Protection in a Murine Challenge Model

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