Molecular Evolution of MERS Coronavirus: Dromedaries as a Recent Intermediate Host or Long-Time Animal Reservoir?

Lau, Susanna K. P.; Wong, Antonio C. P.; Lau, Terrence C. K.; Woo, Patrick C. Y.

The 219 complete genomes of MERS-CoV were clustered into two major clades, A and B ( Figure 2 ). Most MERS-CoV strains belong to clade B, while clade A only contains five strains. Clade A is further divided into two lineages: lineage A1, with three human strains, one being the first MERS-CoV strain isolated from the index 60-year-old male patient from Bisha, Saudi Arabia in September 2012, and the other two from Jordan; and lineage A2, with two camel strains, one from the UAE and the other from Egypt. Clade B is further divided into six lineages. Both human and camel strains were present in most lineages. Lineage B1 is dominated by MERS-CoV strains from the UAE, whereas lineages B2 to B6 are mainly dominated by strains from Saudi Arabia. Lineage 3 consists of the largest number of strains, including the human strains from an outbreak in South Korea, which occurred as a result of acquisition of MERS-CoV by a Korean who visited multiple Middle East countries, including Bahrain, Qatar, Saudi Arabia, and the UAE from 24 April to 4 May 2015 and subsequent spread the infection after returning to South Korea [14] . The same strain of MERS-CoV was also carried to China by a 44-year-old male Korean [15] . This patient visited his father and sister, who were infected with MERS-CoV in South Korea, before traveling to Hong Kong on 26 May and subsequently to Huizhou in the Guangdong province through Shenzhen City. spread the infection after returning to South Korea [14] . The same strain of MERS-CoV was also carried to China by a 44-year-old male Korean [15] . This patient visited his father and sister, who were infected with MERS-CoV in South Korea, before traveling to Hong Kong on 26 May and subsequently to Huizhou in the Guangdong province through Shenzhen City. Fifteen MERS-CoV strains, including six from human and nine from dromedaries, fell into different lineages in the phylogenetic trees constructed using ORF1ab and S (Table 1 and Figure 3 ), suggesting possible recombination events. For example, four MERS-CoV strains from dromedaries (accession numbers KT368829, KT368830, KT368831, KT368832) belong to lineage B5 in the ORF1ab tree but lineage B3 in the S tree; and three MERS-CoV strains from human (accession numbers KT861627, KJ156910, KJ156874) belong to lineage B2 in the ORF1ab tree but lineage B4 in the S tree. Fifteen MERS-CoV strains, including six from human and nine from dromedaries, fell into different lineages in the phylogenetic trees constructed using ORF1ab and S (Table 1, Figure S1 and Figure 3 ), suggesting possible recombination events. For example, four MERS-CoV strains from dromedaries (accession numbers KT368829, KT368830, KT368831, KT368832) belong to lineage B5 in the ORF1ab tree but lineage B3 in the S tree; and three MERS-CoV strains from human (accession numbers KT861627, KJ156910, KJ156874) belong to lineage B2 in the ORF1ab tree but lineage B4 in the S tree. Comparison of the amino acid sequences of the various lineages of MERS-CoV revealed that the number of changes in the S proteins is higher than in other proteins. Notably, MERS-CoV of lineage A2 showed 14 amino acid changes compared to other lineages, while most other lineages (A1, B2-6) only showed one amino acid change compared to other lineages ( Figure 4 ). These amino acid changes are not concentrated in particular motifs ( Figure 4 ).