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      Virus genomes reveal factors that spread and sustained the Ebola epidemic

      research-article
      1 , 2 , 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 5 , 9 , 13 , 14 , 8 , 5 , 15 , 12 , 16 , 17 , 12 , 18 , 19 , 20 , 8 , 21 , 7 , 22 , 7 , 7 , 23 , 24 , 23 , 24 , 14 , 25 , 26 , 27 , 24 , 8 , 28 , 9 , 7 , 8 , 29 , 7 , 9 , 27 , 7 , 30 , 14 , 13 , 14 , 25 , 14 , 8 , 31 , 7 , 32 , 33 , 7 , 34 , 35 , 36 , 14 , 37 , 12 , 9 , 11 , 12 , 23 , 24 , 13 , 7 , 38 , 8 , 31 , 7 , 22 , 7 , 22 , 37 , 12 , 7 , 22 , 39 , 40 , 41 , 19 , 18 , 12 , 42 , 26 , 43 , 44 , 45 ,   46 , 28 , 47 ,   48 , 9 , 27 , 17 , 12 , 49 , 50 ,   51 , 24 , 52 , 13 , 53 , 14 , 54 , 30 , 55 , 45 , 38 , 43 , 8 , 6 , 7 , 22 , 20 , 38 , 21 , 56 , 57 , 58 , 5 , 1 , 59 , 60
      Nature
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The 2013–2016 epidemic of Ebola virus disease was of unprecedented magnitude, duration and impact. Analysing 1610 Ebola virus genomes, representing over 5% of known cases, we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already set the seeds for an international epidemic, rendering these measures ineffective in curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing they were susceptible to significant outbreaks but at lower risk of introductions. Finally, we reveal this large epidemic to be a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help inform interventions in future epidemics.

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          Most cited references28

          • Record: found
          • Abstract: found
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          Improving Bayesian population dynamics inference: a coalescent-based model for multiple loci.

          Effective population size is fundamental in population genetics and characterizes genetic diversity. To infer past population dynamics from molecular sequence data, coalescent-based models have been developed for Bayesian nonparametric estimation of effective population size over time. Among the most successful is a Gaussian Markov random field (GMRF) model for a single gene locus. Here, we present a generalization of the GMRF model that allows for the analysis of multilocus sequence data. Using simulated data, we demonstrate the improved performance of our method to recover true population trajectories and the time to the most recent common ancestor (TMRCA). We analyze a multilocus alignment of HIV-1 CRF02_AG gene sequences sampled from Cameroon. Our results are consistent with HIV prevalence data and uncover some aspects of the population history that go undetected in Bayesian parametric estimation. Finally, we recover an older and more reconcilable TMRCA for a classic ancient DNA data set.
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            • Record: found
            • Abstract: found
            • Article: not found

            An unwinding activity that covalently modifies its double-stranded RNA substrate.

            An activity that unwinds double-stranded RNA has been reported to exist in several organisms. We have analyzed the RNA intermediates and final products of the unwinding reaction. Although the RNA becomes sensitive to single strand-specific ribonucleases during the reaction, the duplex is never completely unwound. Furthermore, the base pairing properties of the RNA are permanently altered; the reacted RNA cannot rehybridize to form the original duplex. We demonstrate that during the reaction many, but not all, of the adenosine residues are converted to inosine residues, and we propose that the covalent modification is responsible for the irreversible change in base pairing properties. Possible biological roles for the unwinding/modifying activity, as well as its relevance to antisense RNA experiments, are discussed.
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              • Record: found
              • Abstract: found
              • Article: not found

              The dynamics of measles in sub-Saharan Africa.

              Although vaccination has almost eliminated measles in parts of the world, the disease remains a major killer in some high birth rate countries of the Sahel. On the basis of measles dynamics for industrialized countries, high birth rate regions should experience regular annual epidemics. Here, however, we show that measles epidemics in Niger are highly episodic, particularly in the capital Niamey. Models demonstrate that this variability arises from powerful seasonality in transmission-generating high amplitude epidemics-within the chaotic domain of deterministic dynamics. In practice, this leads to frequent stochastic fadeouts, interspersed with irregular, large epidemics. A metapopulation model illustrates how increased vaccine coverage, but still below the local elimination threshold, could lead to increasingly variable major outbreaks in highly seasonally forced contexts. Such erratic dynamics emphasize the importance both of control strategies that address build-up of susceptible individuals and efforts to mitigate the impact of large outbreaks when they occur.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                27 November 2017
                12 April 2017
                20 April 2017
                03 December 2017
                : 544
                : 7650
                : 309-315
                Affiliations
                [1 ]Institute of Evolutionary Biology, University of Edinburgh, King’s Buildings, Edinburgh, EH9 3FL, UK
                [2 ]Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
                [3 ]WorldPop, Department of Geography and Environment, University of Southampton, Highfield, Southampton SO17 1BJ, UK
                [4 ]Flowminder Foundation, Stockholm, Sweden
                [5 ]Department of Microbiology and Immunology, Rega Institute, KU Leuven – University of Leuven, Leuven, Belgium
                [6 ]Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK
                [7 ]Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
                [8 ]Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
                [9 ]Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK
                [10 ]National Veterinary Institute, Technical University of Denmark, Bülowsvej 27, 1870, Frederiksberg C, Denmark
                [11 ]Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria
                [12 ]The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
                [13 ]Virus Genomics, Wellcome Trust Sanger Institute, Hinxton, UK
                [14 ]Department of Viroscience, Erasmus University Medical Centre, P.O. Box 2040, 300 CA Rotterdam, the Netherlands
                [15 ]National Institute for Infectious Diseases ”L. Spallanzani” – IRCCS, Via Portuense 292, 00149 Rome, Italy
                [16 ]Naval Medical Research Unit 3, 3A Imtidad Ramses Street, Cairo, 11517, Egypt
                [17 ]Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
                [18 ]National Infections Service, Public Health England, Porton Down, Salisbury, Wilts SP4 0JG, UK
                [19 ]Liberian Institute for Biomedical Research, Charlesville, Liberia
                [20 ]Institut Pasteur de Dakar, Arbovirus and Viral Hemorrhagic Fever Unit, 36 Avenue Pasteur, BP 220, Dakar, Sénégal
                [21 ]University of Sierra Leone, Freetown, Sierra Leone
                [22 ]Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
                [23 ]Viral Hemorrhagic Fever Program, Kenema Government Hospital, 1 Combema Road, Kenema, Sierra Leone
                [24 ]Ministry of Health and Sanitation, 4th Floor Youyi Building, Freetown, Sierra Leone
                [25 ]Institute of Infection and Global Health, University of Liverpool, Liverpool L69 2BE, UK
                [26 ]NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, UK
                [27 ]University of Makeni, Makeni, Sierra Leone
                [28 ]Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
                [29 ]University of Bristol, BS8 1TD, UK
                [30 ]Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK
                [31 ]University of Nebraska Medical Center, Omaha, NE, USA
                [32 ]Department of Pediatrics, Section of Infectious Diseases, New Orleans, LA 70112, USA
                [33 ]Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA
                [34 ]Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA
                [35 ]Institut Pasteur, Functional Genetics of Infectious Diseases Unit, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
                [36 ]Génétique Fonctionelle des Maladies Infectieuses, CNRS URA3012, Paris 75015, France
                [37 ]Bundeswehr Institute of Microbiology, Neuherbergstrasse 11, 80937 Munich, Germany
                [38 ]Viral Special Pathogens Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Atlanta, Georgia, USA
                [39 ]The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA
                [40 ]Scripps Translational Science Institute, La Jolla, CA 92037, USA
                [41 ]Ministry of Social Welfare, Gender and Children’s Affairs, New Englandville, Freetown, Sierra Leone
                [42 ]University of Southampton, South General Hospital, Southampton SO16 6YD, UK
                [43 ]Minstry of Health Liberia, Monrovia, Liberia
                [44 ]World Health Organization, Conakry, Guinea
                [45 ]World Health Organization, Geneva, Switzerland
                [46 ]Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK
                [47 ]Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China
                [48 ]Department of Microbiology and Immunology, New Orleans, LA 70112, USA
                [49 ]Department of Biological Sciences, Redeemer’s University, Ede, Osun State, Nigeria
                [50 ]African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer’s University, Ede, Osun State, Nigeria
                [51 ]Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, the University of Sydney, Sydney, NSW 2006, Australia
                [52 ]Ministry of Health Guinea, Conakry, Guinea
                [53 ]Division of Infectious Diseases, Imperial College Faculty of Medicine, London W2 1PG, UK
                [54 ]Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, B-8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
                [55 ]Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée, Conakry, Guinea
                [56 ]Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, CA, USA
                [57 ]Department of Biomathematics David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA
                [58 ]Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA
                [59 ]Centre for Immunology, Infection and Evolution, University of Edinburgh, King’s Buildings, Edinburgh, EH9 3FL, UK
                [60 ]Fogarty International Center, National Institutes of Health, Bethesda, MD, USA
                Author notes
                [* ]Correspondence and requests for materials should be addressed to A.R. ( a.rambaut@ 123456ed.ac.uk ), G.D. ( gdudas@ 123456fredhutch.org ) or P.L. ( philippe.lemey@ 123456rega.kuleuven.be )
                [†]

                The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

                Article
                PMC5712493 PMC5712493 5712493 nihpa922794
                10.1038/nature22040
                5712493
                28405027
                68325590-d21e-4bb5-a216-a8771390a6f9

                Reprints and permissions information is available at www.nature.com/reprints.

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