Preliminary analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) sequences from Korea and China


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Preliminary analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) sequences from Korea and China

8 June 2015
Prepared by members of the WHO-convened “Laboratory Experts for MERS-CoV” with additional data from several research groups (see complete contributors listing in Appendix).

Recent Middle East respiratory syndrome (MERS) cases in Korea and China are thought to have originated from a virus carried by a traveller returning from the Middle East after visits to the Kingdom of Saudi Arabia (KSA), Bahrain, the United Arabic Emirates and Qatar. A MERS-CoV sequence from a patient in Guangdong has been produced by the Chinese CDC (GenBank KT006149) and the MERS- CoV sequence from a patient in Korea (MERS-CoV/KOR/KNIH/002_05_2015, submitted to GenBank) has been produced by the Korea National Institute of Health and ChunLab, Inc.

A preliminary analysis of the two viral genomes supports the following conclusions:

  1. A strict consensus of the Korean and Chinese MERS-CoV sequences clusters closest with viruses obtained from a recent outbreak in Riyadh in February-March 2015 (1) (Figure 1). The Chinese and Korean viruses are however divergent enough from the Riyadh 2015 cluster to potentially be derived from a separate zoonotic event in the Arabian Peninsula. Given the travel history of the Korean index patient (2) to other countries with recent MERS-CoV cases, the originating country cannot be determined with certainty. From these data the new MERS-CoVs are unlikely to be phenotypically different from the MERS-CoV currently circulating in the Arabian Peninsula and are unlikely to present different virulence or transmission properties. However, further clinical, epidemiological and virus genetic data will be required to be certain of these preliminary conclusions. In addition, there is an urgency to increase sequencing efforts in all countries where MERS-CoV is circulating. This will increase our knowledge of transmission patterns and inform public health measures required to prevent transmission.

  2. The two currently available sequences from Korea and China are from patients with a direct epidemiological link and as such are not expected to show many nucleotide differences. However, it is important to note that the Korean sequence was obtained from a cell culture passaged virus while the Chinese sequence was obtained by direct sequencing of patient swab material. In addition, different error rates and profiles for the sequencing platforms used (Sanger and Ion Torrent for the Chinese sequence versus Illumina for the Korean sequence) and differences in the assembly methods could be a factor. We therefore assume that most of the differences between the Korean and Chinese sequences are the result of these technical issues. Further sequencing will clarify this. These considerations led us to use a strict consensus sequence in the analyses above.

  3. No shared amino changes in the encoded spike were observed between the Korean and Chinese sequences. If there was a more transmissible virus emerging in Korea/China and this was due to a new spike variant, then one would expect the changes to be shared by the two sequences. This was not observed. Additional sequencing of patient samples in Korea will help to resolve the sequence diversity within this cluster.

Figure 1 | Phylogenetic reconstruction of 171 available MERS CoV sequences. A strict consensus was created between the Korean and Chinese sequences (marked in red with asterisk), recent virus sequences from Riyadh (Riyadh KKUH 2015) are from (1) and viruses sequences from camels are shown in orange. Colored boxes indicate previously-defined clades or lineages. The Al-Hasa hospital outbreak is collapsed for clarity. Clade support is shown where the bootstrap support values were greater than 75%. The scale bar is in units of substitutions/site. A maximum-likelihood phylogeny was constructed from the alignment of 171 MERS CoV sequences using RAxML version 7.8.6 under a GTR+G substitution model. Clade support was assessed by bootstrapping with 1000 pseudo- replicates.

References

  1. Somily A, Barry M, Al Subaie SS, BinSaeed AA, Alzamil FA, Zaher W, Al Qahtani T, Al Jerian K, McNabb SJN, Cotten M, Watson SJ, Binter S, Rambaut A, Kellam P. 2015. New MERS- CoV sequences Feb-Mar 2015 and preliminary analysis MERS coronavirus. http://wwwvirologicalorg/t/new-mers-cov-sequences-feb-mar-2015-and-preliminary-analysis/140.
  2. ProMED-mail. 2015. South Korea, new contact cases, media report. http://wwwpromedmailorg/directphp?id=201505223378310.

Appendix.
This summary was prepared with contributions from the following (in alphabetical order):
Imad A. Al-Jahdali, Deputy Minister. Ex.General Director King Fahad General Hospital, Jeddah and Occupational and environmental medicine, Um AlQura University, Kingdom of Saudi Arabia
Khaldoon Al Jerian, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia Ahmed M. Alotaibi, Department of Intensive Care, Prince Mohammed bin Abdulaziz Hospital, Riyadh,
Kingdom of Saudi Arabia
Sarah S. Al Subaie, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia Fahad A. Alzamil, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
Mazin Barry, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
Nahid A. Batarfi PhD, Epidemiology section, Command and Control Center (CCC) Ministry of Health, Jeddah, Kingdom of Saudi Arabia
Abdulaziz A. BinSaeed, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia Špela Binter, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Sylvie Briand, World Health Organization
Yong-Joon Cho, ChunLab, Inc., Seoul National University, South Korea
Jongsik Chun, ChunLab, Inc., Seoul National University, South Korea
Guy Cochrane, EBI, Hinxton, United Kingdom
Victor Corman, Institute of Virology University of Bonn
Matthew Cotten, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Christian Drosten, Institute of Virology University of Bonn
Patrick Anthony Drury, World Health Organization
Pierre B.H. Formenty, World Health Organization
Keiji Fukuda, World Health Organization
George Gao, China CDC, Key Laboratory of Pathogenic Microbiology and Immunology, Institute of
Microbiology, Chinese Academy of Sciences, Beijing, P.R.China
Bart Haagmans, Erasmus Medical Center, Rotterdam, The Netherlands
Paul Kellam, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, Division of Infection and
Immunity, University College London, London, United Kingdom
Sung Soon Kim, Division of Respiratory Viruses, Center for Infectious Diseases, Korea National
Institute of Health, South Korea
You-Jin Kim, Division of Respiratory Viruses, Center for Infectious Diseases, Korea National Institute
of Health, South Korea
Mary K. Kindhauser, World Health Organization
Franciscus Adrianus Jacobus Konings, World Health Organization
Marion Koopmans, Erasmus Medical Center, Rotterdam, The Netherlands
Chin-Kei Lee, World Health Organization
Christian Lindmeier, World Health Organization
Roujian Lu, Key Laboratory of Medical Virology, Ministry of Health, National Institute for
Viral Disease Control and Prevention, China CDC, Beijing, P.R.China
Jaouad Mahjour, World Health Organization
Malik Mamunur World Health Organization
Margaux Mathis, World Health Organization
Scott J.N. McNabb, Rollins School of Public Health, Emory University, Atlanta, GA, USA Christopher John Oxenford, World Health Organization
Mark Pallansch, Centers for Disease Control, USA
Malik Peiris, The University of Kong Kong
Leo Poon, The University of Kong Kong
Theeb Al Qahtani, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia V. Stalin Raj, Erasmus Medical Center, Rotterdam, The Netherlands
Andrew Rambaut, Institute of Evolutionary Biology, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh, United Kingdom and Fogarty International Center, NIH, Bethesda, Maryland, USA
Lawrence Everett Rodewald, World Health Organization
Ali M. Somily, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
Anthony Stewart, World Health Organization
Wenjie Tan, Key Laboratory of Medical Virology, Ministry of Health; National Institute for Viral Disease
Control and Prevention, China CDC, Beijing, P.R.China
Martin Robert Taylor, World Health Organization
Maria Van Kerkhove, World Health Organization
Yanqun Wang, Key Laboratory of Medical Virology, Ministry of Health, National Institute for
Viral Disease Control and Prevention, China CDC, Beijing, P.R.China
Simon J. Watson, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Jeong-Sun Yang, Division of Respiratory Viruses, Center for Infectious Diseases, Korea National
Institute of Health, South Korea
Walid Zaher, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia