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

被引:200
作者
Cotten, Matthew [1 ]
Watson, Simon J. [1 ]
Zumla, Alimuddin I. [2 ,3 ,4 ]
Makhdoom, Hatem Q. [5 ]
Palser, Anne L. [1 ]
Ong, Swee Hoe [1 ]
Al Rabeeah, Abdullah A. [2 ]
Alhakeem, Rafat F. [2 ]
Assiri, Abdullah [2 ]
Al-Tawfiq, Jaffar A. [6 ]
Albarrak, Ali [7 ]
Barry, Mazin [8 ]
Shibl, Atef [8 ]
Alrabiah, Fahad A. [9 ]
Hajjar, Sami [9 ]
Balkhy, Hanan H. [10 ]
Flemban, Hesham [11 ]
Rambaut, Andrew [12 ,13 ]
Kellam, Paul [1 ,3 ,4 ]
Memish, Ziad A. [2 ,14 ]
机构
[1] Wellcome Trust Sanger Inst, Hinxton, England
[2] Global Ctr Mass Gatherings Med, Minist Hlth, Riyadh, Saudi Arabia
[3] Univ Coll London Hosp, NHS Fdn Trust, Dept Med Microbiol, London, England
[4] UCL, Div Infect & Immun, London, England
[5] Minist Hlth, Jeddah Reg Lab, Jeddah, Saudi Arabia
[6] Saudi Aramco, Saudi Aramco Med Serv Org, Dhahran, Saudi Arabia
[7] Prince Sultan Mil Med City, Riyadh, Saudi Arabia
[8] King Saud Univ, Riyadh, Saudi Arabia
[9] King Faisal Specialist Hosp & Res Ctr, Riyadh, Saudi Arabia
[10] King Abdul Aziz Med City, Riyadh, Saudi Arabia
[11] Alhada Mil Hosp, Riyadh, Saudi Arabia
[12] Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland
[13] Fogarty Int Ctr, NIH, Bethesda, MD USA
[14] Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia
基金
英国惠康基金;
关键词
CLINICAL-FEATURES; SARS-CORONAVIRUS; DROMEDARY CAMELS; SAUDI-ARABIA; FUSION CORE; MERS-COV; RECEPTOR; DOMAIN; DETERMINANTS; MECHANISMS;
D O I
10.1128/mBio.01062-13
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 x 10(-3) substitutions per site per year (95% credible interval [95% CI], 8.76 x 10(-4); 1.37 x 10(-3)) 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-0) for the virus that is less than 1. IMPORTANCE 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.
引用
收藏
页数:11
相关论文
共 44 条
[1]   Investigation of Anti-Middle East Respiratory Syndrome Antibodies in Blood Donors and Slaughterhouse Workers in Jeddah and Makkah, Saudi Arabia, Fall 2012 [J].
Aburizaiza, Asad S. ;
Mattes, Frank M. ;
Azhar, Esam I. ;
Hassan, Ahmed M. ;
Memish, Ziad A. ;
Muth, Doreen ;
Meyer, Benjamin ;
Lattwein, Erik ;
Mueller, Marcel A. ;
Drosten, Christian .
JOURNAL OF INFECTIOUS DISEASES, 2014, 209 (02) :243-246
[2]  
AlBarrak AM, 2012, SAUDI MED J, V33, P1265
[3]  
[Anonymous], 2014, MIDDL E RESP SYNDR C
[4]   Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus [J].
Assiri, Abdullah ;
McGeer, Allison ;
Perl, Trish M. ;
Price, Connie S. ;
Al Rabeeah, Abdullah A. ;
Cummings, Derek A. T. ;
Alabdullatif, Zaki N. ;
Assad, Maher ;
Almulhim, Abdulmohsen ;
Makhdoom, Hatem ;
Madani, Hossam ;
Alhakeem, Rafat ;
Al-Tawfiq, Jaffar A. ;
Cotten, Matthew ;
Watson, Simon J. ;
Kellam, Paul ;
Zumla, Alimuddin I. ;
Memish, Ziad A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (05) :407-416
[5]   Improving the Accuracy of Demographic and Molecular Clock Model Comparison While Accommodating Phylogenetic Uncertainty [J].
Baele, Guy ;
Lemey, Philippe ;
Bedford, Trevor ;
Rambaut, Andrew ;
Suchard, Marc A. ;
Alekseyenko, Alexander V. .
MOLECULAR BIOLOGY AND EVOLUTION, 2012, 29 (09) :2157-2167
[6]   SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing [J].
Bankevich, Anton ;
Nurk, Sergey ;
Antipov, Dmitry ;
Gurevich, Alexey A. ;
Dvorkin, Mikhail ;
Kulikov, Alexander S. ;
Lesin, Valery M. ;
Nikolenko, Sergey I. ;
Son Pham ;
Prjibelski, Andrey D. ;
Pyshkin, Alexey V. ;
Sirotkin, Alexander V. ;
Vyahhi, Nikolay ;
Tesler, Glenn ;
Alekseyev, Max A. ;
Pevzner, Pavel A. .
JOURNAL OF COMPUTATIONAL BIOLOGY, 2012, 19 (05) :455-477
[7]   The coronavirus spike protein is a class I virus fusion protein: Structural and functional characterization of the fusion core complex [J].
Bosch, BJ ;
van der Zee, R ;
de Haan, CAM ;
Rottier, PJM .
JOURNAL OF VIROLOGY, 2003, 77 (16) :8801-8811
[8]   Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk [J].
Breban, Romulus ;
Riou, Julien ;
Fontanet, Arnaud .
LANCET, 2013, 382 (9893) :694-699
[9]   Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility [J].
Cauchemez, Simon ;
Fraser, Christophe ;
Van Kerkhove, Maria D. ;
Donnelly, Christi A. ;
Riley, Steven ;
Rambaut, Andrew ;
Enouf, Vincent ;
van der Werf, Sylvie ;
Ferguson, Neil M. .
LANCET INFECTIOUS DISEASES, 2014, 14 (01) :50-56
[10]   Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study [J].
Cotten, Matthew ;
Watson, Simon J. ;
Kellam, Paul ;
Al-Rabeeah, Abdullah A. ;
Makhdoom, Hatem Q. ;
Assiri, Abdullah ;
Al-Tawfiq, Jaffar A. ;
Alhakeem, Rafat F. ;
Madani, Hossam ;
AlRabiah, Fahad A. ;
Al Hajjar, Sami ;
Al-Nassir, Wafa N. ;
Albarrak, Ali ;
Flemban, Hesham ;
Balkhy, Hanan H. ;
Alsubaie, Sarah ;
Palser, Anne L. ;
Gall, Astrid ;
Bashford-Rogers, Rachael ;
Rambaut, Andrew ;
Zumla, Alimuddin I. ;
Memish, Ziad A. .
LANCET, 2013, 382 (9909) :1993-2002