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mBio. Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus

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  • mBio. Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus

    [Source: mBio, full page: (LINK). Abstract, edited.]

    Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus

    Matthew Cotten<SUP>a</SUP>, Simon J. Watson<SUP>a</SUP>, Alimuddin I. Zumla<SUP>b,c,d</SUP>, Hatem Q. Makhdoom<SUP>e</SUP>, Anne L. Palser<SUP>a</SUP>, Swee Hoe Ong<SUP>a</SUP>, Abdullah A. Al Rabeeah<SUP>b</SUP>, Rafat F. Alhakeem<SUP>b</SUP>, Abdullah Assiri<SUP>b</SUP>, Jaffar A. Al-Tawfiq<SUP>f</SUP>, Ali Albarrak<SUP>g</SUP>, Mazin Barry<SUP>h</SUP>, Atef Shibl<SUP>h</SUP>, Fahad A. Alrabiah<SUP>i</SUP>, Sami Hajjar<SUP>i</SUP>, Hanan H. Balkhy<SUP>j</SUP>, Hesham Flemban<SUP>k</SUP>, Andrew Rambaut<SUP>l,m</SUP>, Paul Kellam<SUP>a,c,d</SUP>, Ziad A. Memish<SUP>b,n</SUP>
    <SUP>a</SUP>Wellcome Trust Sanger Institute, Hinxton, United Kingdom - <SUP>b</SUP>Global Centre for Mass Gatherings Medicine (GCMGM), Ministry of Health, Riyadh, Kingdom of Saudi Arabia - <SUP>c</SUP>Department of Medical Microbiology, University College London Hospitals NHS Foundation Trust, London, United Kingdom - <SUP>d</SUP>Division of Infection and Immunity, University College London, London, United Kingdom - <SUP>e</SUP>Jeddah Regional Laboratory, Ministry of Health, Jeddah, Kingdom of Saudi Arabia - <SUP>f</SUP>Saudi Aramco Medical Services Organization, Saudi Aramco, Dhahran, Kingdom of Saudi Arabia - <SUP>g</SUP>Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia - <SUP>h</SUP>King Saud University, Riyadh, Kingdom of Saudi Arabia - <SUP>i</SUP>King Faisal Specialist Hospital, Riyadh, Kingdom of Saudi Arabia - <SUP>j</SUP>King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia - <SUP>k</SUP>Alhada Military Hospital, Riyadh, Kingdom of Saudi Arabia - <SUP>l</SUP>Institute of Evolutionary Biology, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh, United Kingdom - <SUP>m</SUP>Fogarty International Center, NIH, Bethesda, Maryland, USA - <SUP>n</SUP>College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia

    Address correspondence to Ziad A. Memish, zmemish{at}

    M.C., S.J.W., A.I.Z., P.K., and Z.A.M. contributed equally to this work.

    Editor Michael Katze, University of Washington

    doi: 10.1128/mBio.01062-13 - <CITE>18 February 2014 <ABBR>mBio</ABBR> vol. 5 no. 1 e01062-13 </CITE>

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 ? 10<SUP>−3</SUP> substitutions per site per year (95% credible interval [95% CI], 8.76 ? 10<SUP>−4</SUP>; 1.37 ? 10<SUP>−3</SUP>) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R<SUB>0</SUB>) for the virus that is less than 1.


    MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet. While MERS-CoV transmission currently appears weak, careful monitoring of changes in MERS-CoV genomes and of the MERS epidemic should be maintained. The observation of phylogenetically related MERS-CoV in geographically diverse locations must be taken into account in efforts to identify the animal source and transmission of the virus.


    Citation Cotten M, Watson SJ, Zumla AI, Makhdoom HQ, Palser AL, Ong SH, Al Rabeeah AA, Alhakeem RF, Assiri A, Al-Tawfiq JA, Albarrak A, Barry M, Shibl A, Alrabeah FA, Hajjar S, Balkhy HH, Flemban H, Rambaut A, Kellam P, Memish ZA. 2014. Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus. mBio 5(1):e01062-13. doi:10.1128/mBio.01062-13.

    Received 9 December 2013 - Accepted 16 January 2014 - Published 18 February 2014

    Copyright ? 2014 Cotten et al.

    This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.