1. Phenotypic and genetic characterization of MERS coronaviruses from Africa to understand their zoonotic potential
- Author
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Elias Walelign, Malik Peiris, Huibin Lv, Ziqi Zhou, Ouafaa Fassi-Fihri, Leo L.M. Poon, Harry Oyas, John M. Nicholls, Rinah Wanglia, Jincun Zhao, Sophie Von Dobschuetz, Yanqun Wang, Ranawaka A.P.M. Perera, Michael C. W. Chan, Eve Miguel, Obadiah Njagi, Ray T.Y. So, Ihab El Masry, Kenrie P Y Hui, Takele Abayneh, Amadou Trarore, Weiwen Liang, Daniel K.W. Chu, Esayas Gelaye, Wilson Kuria, Véronique Chevalier, Chris Ka Pun Mok, Wantanee Kalpravidh, The University of Hong Kong (HKU), National Veterinary Institute [Debre Zeit, Ethiopia] (NVI), Directorate of Veterinary Services [Nairobi, Kenya], Food and Agriculture Organization of the United Nations [Rome, Italie] (FAO), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de l'Environnement et Recherches Agricoles [Ouagadougou] (INERA), Institut de Recherche pour le Développement (IRD), Institut Agronomique et Vétérinaire Hassan II - IAV (MOROCCO) (IAV), The First Affiliated Hospital of Guangzhou Medical University (GMU), The research was funded by the Commissioned Research on Control of Infectious Diseases (phase III and IV) from the Health and Medical Research Fund, Hong Kong Special Administrative Region, Health and Medical Research Fund Grant 19181032, NIH (Contract HHSN272201400006C and U01 Grant AI151810), a Calmette and Yersin scholarship from the Pasteur International Network Association, and Guangdong Province International Scientific and Technological Cooperation Projects (Grant 2020A0505100063). Field studies in Kenya and Ethiopia were supported through the FAO of the United Nations project OSRO/GLO/505/USA, which is funded by the US Agency for International Development (USAID), Centre national de la recherche scientifique et technologique [Ouagadougou] (CNRST), and Institut Agronomique et Vétérinaire Hassan II (IAV Hassan II)
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Coronaviridae ,Middle East respiratory syndrome coronavirus ,phenotype ,Dipeptidyl Peptidase 4 ,viruses ,coronaviruses ,[SDV]Life Sciences [q-bio] ,Biology ,Virus Replication ,L73 - Maladies des animaux ,medicine.disease_cause ,Microbiology ,Cell Line ,MERS-CoV ,Viral entry ,Zoonoses ,Pandemic ,parasitic diseases ,medicine ,Animals ,Humans ,characterization ,Gene Knock-In Techniques ,Clade ,Phylogeny ,Multidisciplinary ,Zoonotic Infection ,Arabia ,Strain (biology) ,Biological Sciences ,biology.organism_classification ,Virology ,humanities ,Kinetics ,Coronavirus du syndrome respiratoire du Moyen-Orient ,Viral replication ,S50 - Santé humaine ,Spike Glycoprotein, Coronavirus ,Lentivirus ,Africa ,Middle East Respiratory Syndrome Coronavirus - Abstract
Significance The absence of zoonotic MERS-CoV in Africa in spite of an abundance of MERS-CoV–infected dromedaries has remained an enigma. We demonstrate that geographically and genetically distinct viruses from Africa have low replication competence in the human lung, providing a possible explanation for the absence of severe MERS disease in Africa. The findings suggest that MERS-CoV now entrenched in the Arabian Peninsula has acquired increased pathogenic potential for humans. We demonstrate that the spike protein contributes to this phenotypic difference. If pathogenic clade B viruses from the Arabian Peninsula are introduced into Africa, they are likely to become dominant, as they have in the Arabian Peninsula, and to be associated with adverse health impacts in Africa and increased pandemic threat., Coronaviruses are pathogens of pandemic potential. 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. More than 70% of MERS-CoV–infected dromedaries are found in East, North, and West Africa, but zoonotic MERS disease is only reported from the Arabian Peninsula. We compared viral replication competence of clade A and B viruses from the Arabian Peninsula with genetically diverse clade C viruses found in East (Egypt, Kenya, and Ethiopia), North (Morocco), and West (Nigeria and Burkina Faso) Africa. Viruses from Africa had lower replication competence in ex vivo cultures of the human lung and in lungs of experimentally infected human-DPP4 (hDPP4) knockin mice. We used lentivirus pseudotypes expressing MERS-CoV spike from Saudi Arabian clade A prototype strain (EMC) or African clade C1.1 viruses and demonstrated that clade C1.1 spike was associated with reduced virus entry into the respiratory epithelial cell line Calu-3. Isogenic EMC viruses with spike protein from EMC or clade C1.1 generated by reverse genetics showed that the clade C1.1 spike was associated with reduced virus replication competence in Calu-3 cells in vitro, in ex vivo human bronchus, and in lungs of hDPP4 knockin mice in vivo. These findings may explain why zoonotic MERS disease has not been reported from Africa so far, despite exposure to and infection with MERS-CoV.
- Published
- 2021