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Bisha Bat Match Raises MERS-CoV Concerns
Recombinomics Commentary 19:00
August 27, 2013

Reusken notes that the study authors could sequence only a 190-nucleotide-long segment of the 30,000-nucleotide coronavirus genome. Studies have suggested that sequences of at least 800 nucleotides are necessary to accurately determine how closely viruses are related.

The above comments on the recently described 203 nt fragment from a bat in Bisha in the Kingdom of Saudi Arabia,
Taper/CII_KSA_287/Bisha/Saudi Arabia/2012, cites a 2010 study which was written prior to the discovery of MERS-CoV or the publication of large segments of the MERS-CoV genome generated from samples from 10 patients.  Sequences from nine of the cases are complete (each over 30,000 nt) as well as a larger partial sequence (over 5,000 nt), which are in addition to much shorter segments from 4 additional cases. 

All of the human sequences are closely related to each other and are >99.5% identical to the consensus sequence, and are easily distinguished from prior bat sequences, which were <92.5% identical, even when short conserved regions were compared.  Thus, distinguishing these earlier bat sequences from all human sequences was straight forward.

In contrast, the 203 nt sequences is identical to the human sequence, EMC/12 from Bisha, clearly signaling a common origin for the two sequences.  Comments from Ian Lipkin, strongly suggest the identity is not an artifact, since the sequence was generated prior to the acquisition of the human EMC/12 samples and repeated testing of other bat samples have been uniformly negative.

The identity between the Bisha bat and human sequences is significant.  The human sequences can be clearly divided into two sub-clade.  The two earliest sequences (Jordan-N3 from an ICU nurse, 40F, in Jordan and EMC/12 from the first confirmed case, 60M, from Bisha) form one subclade, which differs from the consensus sequence due to clustered polymorphisms in the RNA dependent RNA polymerase (RdRp) gene, most of which are shared by the two earliest sequences.  However, in addition to these shared polymorphisms in RdRp, each sequence has a number of unique polymorphisms. In contrast, the remaining sequences which are largely from cases in the east (Al Hasa in KSA,
Al-Hasa_1, Al-Hasa_2, Al-Hasa_3, Al-Hasa_4), as well as case from Qatar and United Arab Emirates).

The Bisha bat sequence is in RdRp (positions 15057-15259) and each of the two early sequences has a unique polymorphism in this region (T15196C for EMC/12 and C15229T for Jordan-N3).  In contrast, all of the other eight human sequences exactly match the consensus for positions 15057-15259).  Like EMC/12, the Bisha bat sequence has one polymorphism in this region, which is T15196C.  Thus, the sharing of this unique polymorphisms by the human case from Bisha and the bat sequence from Bisha signals a common geographic origin, which has significant implications.

The species for the Bisha bat, Taphozous perforates, has a very limited geographic reach in KSA (which is largely limited to the area surrounding Bisha).  In contrast, this species is far more common in Egypt and Sudan in Africa, as well as India in Asia, raising the possibility that related MERS-CoV cases are grossly under-reported in these countries (none have reported a MERS-CoV case within their borders).  Moreover the exact match between the Bisha sequences suggest that many additional bat sequences have sequences closely related to the human cases, which signal multiple independent introductions.

However, the 10 published sequences represent a small percentage of the confirmed cases and the diversitry may be significantly higher.  21 additional human sequences are expected to be released in the near term, and are said to be diverse and signal more independent introductions.

These published and soon to be released sequences suggest that there should be a greater effort targeting bat droppings, which have a high concentration of coronavirus RNA,, and were the source of the match in the Bisha bat.  In the past coronavirus sequences have been identified in collections represent 1000’s or tens of 1000’s samples of bat droppings, which can be efficiently collected to determine the diversity of closely related MERS-CoV sequences in bats in KSA. 

Those sequences can be used with the expanded sequence database from human cases to determin the role of bats in the “sporadic” cases, and follow up studies which include bat captures and wing punches can be used to link the diverse sequences to specific bat species and geographic distribution.

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