Abstract
ABSTRACTThe 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 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 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 (R0) for the virus that is less than 1.
Highlights
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
The SARS coronavirus emerged from an animal reservoir [6], and a zoonotic event may provide the source of MERS-CoV; no consistent pattern of animal exposure has been observed with MERS cases
All PCR-confirmed MERS case samples from Saudi Arabia were processed for whole-genome deep sequencing [14, 15], adding 32 new MERS-CoV genome sequences to the publically available data set
Summary
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. We have determined the MERSCoV 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. The Middle East Respiratory Syndrome Coronavirus (MERSCoV) was first detected in the Kingdom of Saudi Arabia (KSA) in 2012 [1,2,3,4], and to date, infection with the virus has been identified in 180 patients with 43% mortality [5]. We advance our knowledge of the MERS-CoV outbreak with complete or partial MERS-CoV genome sequences obtained directly from 32 recent MERS patient samples from cases between July and September 2013, bringing the total available MERS-CoV genomic sequences to 65 (37% of the 178 MERS cases reported globally)
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