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UK 2013 Beta Coronavirus Cluster Sequence
Recombinomics Commentary 17:30
February 23, 2013

Phylogenetic Tree

The Health Protection Agency (HPA) phylogenetic tree of novel beta coronavirus Whole Genome Sequences (WGS) linked above includes the sequence from the index case (60M who developed symptoms on January 24, 2013 while practicing Umrah in Saudi Arabia) of the recent UK cluster (designated England2 in the red box).  As seen in the above tree it is virtually identical to the first confirmed case (60M) who died at a hospital in Jeddah (disease onset date of June 13, 2012), who was confirmed and sequenced by Erasmus Medical Center (designated as EMC2012) as well as the second case who first developed symptoms while practicing Umrah in Saudi Arabia in August 2012 (designated as England1).  As noted by HPA, the newly released sequence has a 99.6% identity with the other two WGS representations.  The only other group 2c WGS are also in the tree.  Both series (HKU5 and HKU4) are from bats in Guangdong province.  Although both sets of bat sequences have some degree of relatedness to each other within group 2c, they are distinct from the human sequences.  Therefore, while the bat sequences are those that are most closely related to the human sequences (no group 2c sequences have been identified in any species other than bats), they are not closely related to the human sequences.  All of the sequences closely related to each of the human sequences are other human sequences.

In addition the WG sequences above, partial sequences have been obtained for two other cases. 

Sequences were generated for two regions of an isolate from a gym teacher (45M) from Riyadh.  The sequences were described in a paper while included authors from the Saudi Arabia Ministry of Health.  In the paper, both sequences were identical to EMC2012.  Subsequently, the two sequences in the above tree were released, and both HPA sequences were also identical.  Thus, the two regions represented by the Riyadh isolate were identical to all three of the above human sequences. In contrast the closest bat sequences were 83% and 78% identical, demonstrating significant divergence. 

Similar results were seen for partial sequences from two other regions from an isolate from a Qatari case treated in Germany.  Those sequences from the Essen isolate were also virtually identical to the above sequences.  One region had an 88% identity with a bat group 2c sequence from Romania (it had an identity of 82% with the most closely related sequence from the HKU5 series).  That region exactly matched the England1 and England2 sequences, and differed at a single position from EMC2012.  Similarly, the second region (which was not closely related to any coronavirus sequence other than novel human sequences listed above), differed from EMC2012 and England2 (England1 had a 6 bp deletion in this region, which was not present in any of the other three sequences).

Thus, all five sets of sequences from human cases were virtually identical to each other, but readily distinguished from sequences from various samples from bat species in Asia, Europe, and Africa. 

The latest human sequence represents the first reported sequence from 2013, as well as the first sequence from a confirmed cluster.  However, it is closely related to sequences as early as the summer of 2012, as well as the other confirmed cases, including those from the spring of 2012 from fatal cases in Jordan, which were identified with PCR tests specific for the human sequences depicted in the three samples in the phylogentic tree. 

Thus, the sequences full support human to human transmission of a novel beta coronavirus, which has not been reported in any species, including bats.

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