Zoonotic origin and transmission of Middle East respiratory syndrome coronavirus in the UAE

Abstract

Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, there have been a number of clusters of human-to-human transmission. These cases of human-to-human transmission involve close contact and have occurred primarily in healthcare settings, and they are suspected to result from repeated zoonotic introductions. In this study, we sequenced whole MERS-CoV genomes directly from respiratory samples collected from 23 confirmed MERS cases in the United Arab Emirates (UAE). These samples included cases from three nosocomial and three household clusters. The sequences were analysed for changes and relatedness with regard to the collected epidemiological data and other available MERS-CoV genomic data. Sequence analysis supports the epidemiological data within the clusters, and further, suggests that these clusters emerged independently. To understand how and when these clusters emerged, respiratory samples were taken from dromedary camels, a known host of MERS-CoV, in the same geographic regions as the human clusters. Middle East respiratory syndrome coronavirus genomes from six virus-positive animals were sequenced, and these genomes were nearly identical to those found in human patients from corresponding regions. These data demonstrate a genetic link for each of these clusters to a camel and support the hypothesis that human MERS-CoV diversity results from multiple zoonotic introductions.

Keywords: dromedary camel; epidemiology; genomics; middle east respiratory syndrome; viral pathogens; zoonoses.

Figure 1

Geographic distribution of human and camel cases in the UAE, 2013–2014. Map of the United Arab Emirates showing approximate location of each sequenced human MERS case, as well as the location of the Middle East respiratory syndrome coronavirus (MERS‐CoV)‐positive camels sampled in this study. Each marker represents an individual case sequenced in this study. Arrows represent the importation of cases to the indicated location. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Summary of cases sequenced from the UAE 2013–2014 clusters. Each Middle East respiratory syndrome coronavirus (MERS‐CoV) genome sequenced from the UAE clusters is shown as a circle. Filled circles represent those human samples where full MERS‐CoV genome sequence was obtained, stripe‐filled circles represent where only S and N gene sequences were obtained. Triangles represent associated MERS cases where no sequence was obtained. Cases are plotted along a timeline corresponding with the index case infection date, and those associated with frequent exposure to camels are in the shaded region. Camels that were directly implicated in a cluster are connected by a solid arrow. Human cases where the sequence indicates that there is significant similarity to a camel are connected by a dashed arrow. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Genome alignment and Single nucleotide polymorphism (SNPs) within UAE cases. (a) Full genome sequences or (b) S gene nucleotide sequences from the 2013–2014 UAE Middle East respiratory syndrome coronavirus clusters, sporadic cases and camels were aligned with parsnp, using Human betacoronavirus 2c EMC/2012 (GenBank JX869059) as a reference sequence. Gingr was used to visualize SNPs, compared to the reference genome. Each vertical bar in the graph represents a single SNP. Asterisks in S gene alignment represent amino acid changes

Figure 4

PhyML tree analysis of Middle East respiratory syndrome coronavirus (MERS‐CoV) genome sequences. Maximum likelihood tree 97 MERS‐CoV genomes, generated using PhyML. The trees include sequences from the 2013–2014 UAE clusters as well as camel‐derived viruses sequenced in this study and representative sequences from GenBank. The lineages described in Sabir et al. are indicated. The clusters described in the paper are highlighted in coloured boxes. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

BEAST time‐scaled tree of Middle East respiratory syndrome coronavirus (MERS‐CoV) cases. After filtering recombinant MERS‐CoV genomes using RDP, the remaining genomes were analysed using BEAST to understand divergence times between the various human cases and between the human and camel cases. Node A shows a divergence between a camel virus and the 2014_008‐associated cluster (Healthcare‐associated clusters III and HH C) virus that occurred separately, but concurrent, with the divergence at Node C, between a camel virus and human case 2014_XXX. Likewise, the divergence of the 2014_002 virus from a camel virus happened at Node B, separately and later than the other two examples. The clusters described in the paper are highlighted in coloured boxes. [Colour figure can be viewed at http://wileyonlinelibrary.com]