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

Calu-3 cells, a human adenocarcinoma cell line of bronchial epithelial origin that retains innate immune function, were infected at a multiplicity of infection (MOI) of 0.01. EMC and AH13 strains replicated comparably with each other, while BF785 and Nig1657 replicated to significantly lower titer at 24 and 48 h postinfection ( Fig. 2A) and area-under-curve (AUC) analysis (Fig. S5A) . Similar observations were made in Calu-3 cells infected at an MOI of 0.1 with EMC, AH13, and BF785 viruses (Fig. S5 B and C) . In experimentally infected C57BL/6 mice made susceptible to infection with MERS-CoV by transducing the human dipeptidyl peptidase receptor (hDPP4) using an adenovirus type 5 vector expressing hDPP4 (14), BF785 viral titers in the lung were significantly lower than EMC or AH13 virus titers at both day 3 and day 5 post infection, the difference in viral titers being >2log 10 at 3 d post infection (Fig. 2B ), although histology did not reveal obvious differences in pathology (Fig. S6 ). MERS-CoV BF785 and Nig1657 replicated less efficiently than EMC in ex vivo cultures (15) of human bronchus and lung ( Fig. 2C; Fig. S5D shows the AUC). The immunohistochemistry of infected human bronchus and lung did not reveal any obvious difference in tropism (Fig. S5E) .