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

Chu D.K.W., Hui K.P.Y., Perera R.A.P.M., Miguel E., Niemeyer D., Zhao J., Channappanavar R., Dudas G., Oladipo J.O., Traoré A., Fassi-Fihri O., Ali A., Demissie G.F., Muth D., Chan M.C.W., Nicholls J.M., Meyerholz D.K., Kuranga S.A., Mamo G., Zhou Z., So R.T.Y., Hemida M.G., Webby R.J., Roger F., Rambaut A., Poon L.L.M., Perlman S., Drosten C., Chevalier V., Peiris M.. 2018. Proceedings of the National Academy of Sciences of the United States of America, 115 (12) : p. 3144-3149.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal¿human interface. Middle East respiratory syndrome (MERS) remains a disease of global public health concern (1). Many human infections are zoonotic in origin, but some result from clusters of human-to-human transmission, especially within hospitals and health care facilities (2). Zoonotic disease has been reported from the Arabian Peninsula, and dromedary camels are the only confirmed source of zoonotic infection (3). Although MERS-coronavirus (MERS-CoV) is also endemic in dromedaries in Africa, where the majority of dromedary camels are found (4??¿7), zoonotic infections have not been reported from Africa. Hypotheses for this pattern of zoonotic disease include genetic differences in the viruses; cultural, behavioral, or dietary differences in interactions between humans and camels and camel products; or unnoticed human cases through lack of awareness and surveillance in African countries. Data on phylogenetic and phenotypic characterization of MERS-CoV from Africa are limited. We previously reported that MERS-CoV from Egypt and Nigeria appear to be phylogenetically distinct from those currently circulating in the Arabian Peninsula (5, 6). We now report a comprehensive genetic and phenotypic analysis of MERS-CoV from North (Morocco), West (Nigeria, Burkina Faso), and East (Ethiopia) Africa compared with viruses from the Arabian Peninsula. (Résumé d'auteur)

Mots-clés : enquête pathologique; santé publique; surveillance épidémiologique; provenance; transmission des maladies; maladie de l'homme; génotype; phénotype; phylogénie; génétique des populations; dynamique des populations; zoonose; dromadaire; coronavirus; nigéria; Éthiopie; burkina faso; maroc; afrique

Thématique : Maladies des animaux; Autres thèmes

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