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Novel MERS Sub-Clade In Jeddah Raises Pandemic Concerns
Recombinomics Commentary 15:00
April 28, 2014

The release of three nearly full MERS sequences from Jeddah (Jeddah_C7569, Jeddah_C7149, Jeddah_C7770) at the Institute for Virology website prior to publication or release at Genbank is similar to the activity seen in the early stages of the SARS outbreak in April 2003.

Initial reports on SARS were descriptive, but a diagnostic screening tool suggested that the etiological agent was a novel coronavirus, which was subsequently names SARS (Sudden Acute Respiratory Syndrome) which was designated as beta 2b.  The sequence data showed that the international spread of SARS-CoV was associated with a super-spreader event at the Metropole Hotel on February 20-21, 2013, which involved a unique sub-clade with a 29 BP deletion, and almost all human SARS sequences outside of mainland China had this deletion, signaling clonal expansion of this particularly virulent sub-clade..

The recent explosion of MERS cases in Jeddah and associated export has raised concerns that a novel sub-clade has emerged, with increased human transmission.  This concern has led to the early release of three nearly complete MERS sequences from three early collections from patients in two hospitals. 

Phylogenetic analysis showed that all three were closely related to each other and distinct from all public human MERS sequences.  Although the spike protein sequence matches other human sequences, MERS antibodies and sequences have been widely detected in camels in the Middle East and northeast Africa, suggesting MERS is already well adapted to mammals, which was also seen in the first MERS outbreak (in April 2012 in Jordan), which involved human to human transmission among a large number of health care workers.

Thus, the dramatic jump in Jeddah cases may be linked to a single nucleotide change, leading to strong selection and the emergence of a novel subclade, which grows more efficiently in humans.  This sub-clade emergence is supported by partial spike gene sequencing of 25 additional Jeddah cases, which are identical at the protein level, as indicated by Chistian Drosten.
Moreover, a recently complete camel sequence (camel_2) from Qatar (as described in an EID submitted paper, by Bart Haagmans - Andrew Rambaut, personnel communication) is also closely related to the 3 human Jeddah sequence raising the possibility that the sequences from the super-spreader in Abu Dhabi are also related to the Jeddah sequences).

Release of the camel_2 sequence from Qatar, as well as the nucleotide sequences from the 25 additional recent Jeddah cases, would be useful.


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