MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity

Chu, Daniel K. W.; Hui, Kenrie P. Y.; Perera, Ranawaka A. P. M.; Miguel, Eve; Niemeyer, Daniela; Zhao, Jincun; Channappanavar, Rudragouda; Dudas, Gytis; Oladipo, Jamiu O.; Traoré, Amadou; Fassi-Fihri, Ouafaa; Ali, Abraham; Demissié, Getnet F.; Muth, Doreen; Chan, Michael C. W.; Nicholls, John M.; Meyerholz, David K.; Kuranga, Sulyman A.; Mamo, Gezahegne; Zhou, Ziqi; So, Ray T. Y.; Hemida, Maged G.; Webby, Richard J.; Roger, Francois; Rambaut, Andrew; Poon, Leo L. M.; Perlman, Stanley; Drosten, Christian; Chevalier, Veronique; Peiris, Malik

The impact of the different ORF4b deletion events on the functional domains of the putative protein are shown in Fig. S4 . The type i/v deletion found in BF785 and BF434 viruses truncated the ORF4b protein from 246 aa found in the EMC prototype MERS-CoV EMC to 14 aa, deleting the whole of the nuclear localization signal as well as the enzymatic domain that cleaves 2′,5′-oligoadenylate (9) . Nig1657 retains the nuclear localization signal and part of the phosphodiesterase (PDE) domain and is truncated to 71 aa. All these deletions disrupt the PDE catalytic site. ORF4b encoded a polypeptide known to be an IFN antagonist (10, 11) . The N-terminal region of ORF4b encodes the nuclear localization signal. Deletion of this region abrogated nuclear localization and led to a loss of suppression of IFN-β induction via the IRF3-and IRF7-signaling pathways. However, it did not affect suppression of IFN-β via Tank-binding kinase 1 and IκB kinase, which was demonstrated in transient transfection experiments and appears to be mediated by the C-terminal domain of ORF4b (10) . These data come from ORF4b protein overexpression and may or may not be physiologically relevant. The two Saudi Arabian clade B viruses Riyadh_1 and Bisha_1 had less extensive deletions of the PDE domain, although they also disrupt the PDE catalytic site.