Evolving Novel MERS Jeddah Sub-Clade Confirmed In Greece
May 14, 2014
Recently, a novel MERS Jeddah/Mecca sub-clade was reported in six of six cases from four hospitals in Jeddah or Mecca. Moreover, the partial spike gene sequence 25 additional Jeddah cases exactly match the 6 nearly complete sequences. In recent weeks there have been seven Jeddah exports to six countries (Jordan, Malaysia, Greece, United Arab Emirates, Egypt, United States). Another export from the Kingdom of Saudi Arabia (KSA) was announced today (Netherlands – location in KSA not cited).
The United States CDC, in collaboration with the Hellenic Institute, released the Spike and N gene sequences, Greece-Saudi Arabia_2014, from an April 18 oropharyngeal swab from the Jeddah export to Greece (69M), who is in critical condition. The 11 polymorphisms that define the sub-clade include 2 in the spike gene and 3 in ORF8b (which is fully overlapped by the N gene). One of the Spike polymorphisms, Q833R, and one of the ORF8b polymorphisms, have not been reported in any MERS sequences, other than those in the sub-clade described above. The sequences from the exported case had both unique polymorphisms, as well as the other three polymorphisms, which are in these two genes, and partially define the sub-clade, confirming the spread of the Jeddah sub-clade to Greece via commercial airline.
However, the new sequence had two additional polymorphisms that have never been reported previously in MERS sequences. One, R511P, was detected as a mixture in the receptor binding domain region of the Spike gene, while the other polymorphism, T34I, was in ORF8b. Thus, the number of unique polymorphisms has increased from 2 to 4, and all four are non-synonymous.
For ORF8b, which is 112 amino acids in length, there are 4 defining changes, L6Q, T34I, L40P, K60N. Moreover, the CDC also released a full sequence, Indiana/USA-1_Saudi Arabia_2014, for the first confirmed case in the United States, who was a health care worker from Riyadh. That sequence is similar to earlier Riyadh sequences, but has a stop codon at position 78 in ORF8b, truncating the protein to 77 amino acids.
In the SARS outbreak in 2003 virtually all human sequences after the outbreak at the Metropole Hotel on February 20-21 had a 29 nt deletion in ORF8 (creating ORF8a and ORF8b).
The targeting of ORF8b in recent sequences as well as clonal expansion of the Jeddah sub-clade and export to various countries, including Greece, raise serious concerns, as does the rapid evolution of the sub-clade, as seen in the sequences from Greece.