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Novel MERS Jeddah Sub-Clade Defined - Includes Q833R
Recombinomics Commentary 19:00
April 30, 2014

We have sequenced near full genomes of 3 viruses from the early phase of the Jeddah outbreak. The samples were submitted to Jeddah regional laboratory on [3, 5 and 7 Apr 2014], and sent to Germany for external confirmatory testing on [14 Apr 2014] by KSA MOH in Riyadh. Two of the sequenced viruses were from patients treated in the major public hospital in which most cases of the Jeddah outbreak seem to have occurred. A 3rd sequence was from another health care facility in the city. Genome sequences of all 3 viruses are highly similar to each other but not identical,

We have sequenced partial spike protein genes from another 25 viruses, showing 100 percent sequence identity with above-mentioned genomes.

The above comments by Christian Droston, describe three nearly complete MERS sequences from three Jeddah (
Jeddah_C7569, Jeddah_C7149, Jeddah_C7770) cases which were included in the phylogenetic tree published at the Virology Institute website, which also had the sequences for these three cases.  The tree indicated the sequences were novel and formed a sub-clade devoid of prior MERS sequences.

An anysis of the three sequence identified 9 polymorphisms (listed below) which were present in all three sequences from the Jeddah cases, and were not present in any public MERS sequence.  Thus, the 9 markers define the novel MERS sub-clade and raise concerns that one or more of these changes is responsible for the dramatic spike in MERS cases, which have led to at least five exported cases from Jeddah ( to Jordan twice, Malaysia, Greece, and UAE).

None of the 9 changes are non-synonymous in the spike gene (positions 21456-25517),
CORRECTION: A23953G is non-synonymous and encodes Q833R
but these changes clearly identify the novel sub-clade.  Therefore, short sequences (such as positions 28778-28941) should be published to characterize the 25 viruses from Jeddah cases which are cited above.  These cases have identical spike protein sequences, which also match sequences not from the Jeddah sub-clade, although a spike gene sequence from positions 23804-23953 would include two of these unique polymorphisms, including Q833R.

Several of these 9 polymorphisms appear to be present in a camel sequence that was published in a phylogenetic tree published by Andrew Rambaut, based on the presence of Qatar_camel_2 (sequence by Bart Haagmans) on the branch with the 3 human sequences.  The sequences are described in a submitted paper to EID (Andrew Rambaut, personal communication).

It would be useful if the authors published camel_2 and related sequences on their website, as was done for the human sequences cited above, as well as websites of sequencers generating SARS sequences in 2003.

The role and distribution of this novel sub-clade appears to be linked to the explosion of cases in Jeddah, and the similar sequence in a camel in Qatar may be related to the MERS super-spreader (45M) in Abu Dhabi, since his fatal infection may be linked to an earlier fatal case (68M,) at the same hospital, who raised camels.
  9 Polymorphisms Unique to the Three Jeddah Cases

A23953G   (Q833R)

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