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Recombination and 45 New MERS Sequences
Recombinomics Commentary 22:45
September 19, 2013

The Kingdom of Saudi Arabia Ministry of Health has recently released 45 MERS sequences from 21 patients.  Previously, full sequences had been made public from nine patients, which included four sequences from Al Hasa (Al-Hasa 1, 2, 3, 4), which were virtually identical, confirming the clonal expansion spread of MERS in the Al Hasa outbreak (the sequences were >99.99% identical with 0-2 differences with the Al Hasa consensus).  The recent sequences included seven more full sequences from Al Hasa (Al Hasa 12, 15, 16, 17, 18, 19, 21) as well as 32 partial sequences from 8 more Al Hasa patients (Al Hasa 7, 8, 9, 10, 11, 13, 14, 22), which are also virtually identical to the four Al Hasa sequences released previously.

Thus, the newly released 45 sequences had 6 new full sequences not previously represented in the public data base.  Although the new sequence data sheets did not include the age and gender of the patients, the collection date and location allowed for likely assignments, which may be clarified in the upcoming paper in Lancet.  Bisha_1, collected on June 19, 2012 is likely from the same patient (60M) as EMC/12 (although the two sequences were from very distinct sub-clades). Riyadh_1, collected October 23, 2012, is from the gym teacher (45M) who fully recovered (although he was hospitalized for a month and was on hemodialysis due to kidney failure).  Riyadh_2, collected October 30, 2012, is likely from the fatally infected son (39M) in the first family cluster in Riyadh.  Riyadh_3, collected on February 5, 2013 is likely from the fatally infected case (61F) who developed symptoms while in Egypt. Baraidah_1, collected on May 13, 2013, is from the fatally infected case (63M).  Hafr-Al-Batin_1, collected on June 4, 2013, is also from a fatally infected case.

Two of the sequences (Riyadh_2_2012 and Baraidah_1) have polymorphisms that are shared with the Al-Hasa sequences.  However, the other four sequences (Bisha_1_2012 and Riyadh_1_2012, which are virtually identical, Riyadh_3_2013, and Hafr-Al-Batin_1_2013, which has the most complex acquisition pattern) have clear examples of recombination.

The presence of two very distinct sequences in the first confirmed case, indicates MERS is widespread and generates dual infections, which facilitate recombination.  The virtually identity in Bisha_1 and Riyadh_1, collected 4 months apart) signals high fidelity in RNA replication, supporting rapid evolutionary change via recombination.  Moreover, the complex acquisition pattern in Hafr-Al-Batin indicates infections by multiple beta2c coronaviruses are common.

Thus, the recently released sequences suggests that the number of MERS-CoV infections in the Middle East is markedly higher than the modest number of confirmed cases.

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