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MERS ORF8b Truncated In Munster Indiana
Recombinomics Commentary 15:30
May 14, 2014

The 29-nucleotide deletion results in the splitting of a single ORF8ab into two overlapping ORFs, ORF8a and ORF8b. The ORF8ab region encodes for a single protein 8ab of 122 amino acids while ORF8a and ORF8b encode for proteins 8a and 8b of 39 and 84 amino acids, respectively

The above comments on the 29 nt deletion in SARS-CoV in 2003 serves as a reminder of the linkage between a genetic change in one small protein and the explosion and international spread of SARS cases.  This deletion was identified in cases linked to a February stay at the Metropole Hotel.  Tourists of visitors to 13 rooms on the 9th floor (see 9th floor layout) developed SARS symptoms and were linked to superspreader events in hospitals in Hong Kong, Singapore, Hanoi, and Toronto.

MERS-CoV is a coronavirus (beta 2c) that is related to SARS-CoV (beta 2b).  The above ORF (Open Reading Frame) 8 in SARS is adjacent to the N gene, while in MERS it overlaps with N gene.  The encoded protein in MERS is 112 amino acids and the functional relationship between the two gene products is not well understood.

However, changes in ORF8b in MERS have raised serious concerns.  The CDC has released the sequence from the first confirmed MERS case in the United States, Indiana/USA-1_Saudi Arabia_2014, which has a termination codon at position 78 in ORF8b, leading to a truncated protein of 77 amino acids.  This same truncation was found in the sequence of Qatar 3.  In addition to truncating ORF8b, C28996T encodes S144L in the overlapping N gene.

Similarly, the novel sub-clade in Jeddah has three non-synonymous changes in ORF8b (L6Q, L40P, K60N) with the latter also changing the N gene (D126H) raising concerns that the ORB8b is also compromised in the Jeddah sub-clade, which has been confirmed in export to Greece.  The second confirmed case in the United States was from Jeddah, and it is likely that the sequence from this case (44M), will have the changes that define the Jeddah novel sub-clade.

Moreover, the sequence from Indiana has a receptor binding domain change, L411F, in the Spike protein, which has not been reported in prior MERS sequences, and the Jeddah sub-clade also have a novel S gene change, Q833R (also confirmed in Geece), raising serious adaptation and transmission concerns.

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