Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study.
BACKGROUND
Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin.


METHODS
Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85-95%, and four 30-50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done.


RESULTS
Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction.


CONCLUSIONS
We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed.


BACKGROUND
Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.
Wellcome Trust Sanger Institute, Hinxton, UK.
Matthew
M
Cotten
Wellcome Trust Sanger Institute, Hinxton, UK.
Simon J
SJ
Watson
Wellcome Trust Sanger Institute, Hinxton, UK; Division of Infection and Immunity, University College London, London, UK.
Paul
P
Kellam
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia.
Abdullah A
AA
Al-Rabeeah
Jeddah Regional Laboratory, Ministry of Health, Jeddah, Saudi Arabia.
Hatem Q
HQ
Makhdoom
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia.
Abdullah
A
Assiri
Saudi Aramco Medical Services Organisation, Saudi Aramco, Dhahran, Saudi Arabia.
Jaffar A
JA
Al-Tawfiq
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia.
Rafat F
RF
Alhakeem
Jeddah Regional Laboratory, Ministry of Health, Jeddah, Saudi Arabia.
Hossam
H
Madani
King Faisal Specialist Hospital, Riyadh, Saudi Arabia.
Fahad A
FA
AlRabiah
King Faisal Specialist Hospital, Riyadh, Saudi Arabia.
Sami
S
Al Hajjar
Imam Abdulrahman Bin Mohamed Hospital-National Guard Health Affairs-Dammam, Saudi Arabia.
Wafa N
WN
Al-nassir
Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Ali
A
Albarrak
Alhada Military Hospital, Riyadh, Saudi Arabia.
Hesham
H
Flemban
King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Hanan H
HH
Balkhy
Paediatric Infectious Diseases, King Saud University, Saudi Arabia.
Sarah
S
Alsubaie
Wellcome Trust Sanger Institute, Hinxton, UK.
Anne L
AL
Palser
Wellcome Trust Sanger Institute, Hinxton, UK.
Astrid
A
Gall
Wellcome Trust Sanger Institute, Hinxton, UK.
Rachael
R
Bashford-Rogers
Institute of Evolutionary Biology, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh, UK; Fogarty International Center, NIH, Bethesda, MD, USA.
Andrew
A
Rambaut
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia; Division of Infection and Immunity, University College London, London, UK; UCL Hospitals NHS Foundation Trust, London, UK.
Alimuddin I
AI
Zumla
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia. Electronic address: zmemish@yahoo.com.
Ziad A
ZA
Memish
D001483:Base Sequence; D017934:Coronavirus / Q000235:genetics*; D018352:Coronavirus Infections / Q000453:epidemiology / Q000235:genetics* / Q000635:transmission; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005784:Gene Amplification; D016679:Genome, Viral; D006801:Humans; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000235:genetics* / Q000635:transmission; D012529:Saudi Arabia / Q000453:epidemiology; D013577:Syndrome