title: Link of a ubiquitous human coronavirus to dromedary camels.
abstract: The four human coronaviruses (HCoVs) are globally endemic respiratory pathogens. The Middle East respiratory syndrome (MERS) coronavirus (CoV) is an emerging CoV with a known zoonotic source in dromedary camels. Little is known about the origins of endemic HCoVs. Studying these viruses' evolutionary history could provide important insight into CoV emergence. In tests of MERS-CoV-infected dromedaries, we found viruses related to an HCoV, known as HCoV-229E, in 5.6% of 1,033 animals. Human- and dromedary-derived viruses are each monophyletic, suggesting ecological isolation. One gene of dromedary viruses exists in two versions in camels, full length and deleted, whereas only the deleted version exists in humans. The deletion increased in size over a succession starting from camelid viruses via old human viruses to contemporary human viruses. Live isolates of dromedary 229E viruses were obtained and studied to assess human infection risks. The viruses used the human entry receptor aminopeptidase N and replicated in human hepatoma cells, suggesting a principal ability to cause human infections. However, inefficient replication in several mucosa-derived cell lines and airway epithelial cultures suggested lack of adaptation to the human host. Dromedary viruses were as sensitive to the human type I interferon response as HCoV-229E. Antibodies in human sera neutralized dromedary-derived viruses, suggesting population immunity against dromedary viruses. Although no current epidemic risk seems to emanate from these viruses, evolutionary inference suggests that the endemic human virus HCoV-229E may constitute a descendant of camelid-associated viruses. HCoV-229E evolution provides a scenario for MERS-CoV emergence.
authors.affiliation: University of Bonn Medical Centre, 53127 Bonn, Germany; German Centre for Infection Research, partner site Bonn-Cologne, Germany;
authors.forename: Victor M
authors.identifier: 0000-0002-3605-0136
authors.initials: VM
authors.lastname: Corman
authors.affiliation: University of Bonn Medical Centre, 53127 Bonn, Germany;
authors.forename: Isabella
authors.initials: I
authors.lastname: Eckerle
authors.affiliation: College of Medicine, Alfaisal University, 11533 Riyadh, Kingdom of Saudi Arabia;
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Memish
authors.affiliation: International Livestock Research Institute, Nairobi, Kenya;
authors.forename: Anne M
authors.initials: AM
authors.lastname: Liljander
authors.affiliation: Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty Bern, University of Bern, 3012 Bern, Switzerland; Federal Department of Home Affairs, Institute of Virology and Immunology, Bern and Mittelhausern, Switzerland;
authors.forename: Ronald
authors.initials: R
authors.lastname: Dijkman
authors.affiliation: Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty Bern, University of Bern, 3012 Bern, Switzerland; Federal Department of Home Affairs, Institute of Virology and Immunology, Bern and Mittelhausern, Switzerland;
authors.forename: Hulda
authors.initials: H
authors.lastname: Jonsdottir
authors.affiliation: Ministry of Agriculture, Livestock, and Fisheries, State Department of Livestock, Department of Veterinary Services, Nairobi, Kenya;
authors.forename: Kisi J Z
authors.initials: KJ
authors.lastname: Juma Ngeiywa
authors.affiliation: Ministry of Agriculture, Livestock, and Fisheries, State Department of Livestock, Department of Veterinary Services, Nairobi, Kenya;
authors.forename: Esther
authors.initials: E
authors.lastname: Kamau
authors.affiliation: Vétérinaires Sans Frontières Germany, Nairobi, Kenya;
authors.forename: Mario
authors.initials: M
authors.lastname: Younan
authors.affiliation: Ministry of Health, 11176 Riyadh, Kingdom of Saudi Arabia;
authors.forename: Malakita
authors.initials: M
authors.lastname: Al Masri
authors.affiliation: Ministry of Health, 11176 Riyadh, Kingdom of Saudi Arabia;
authors.forename: Abdullah
authors.initials: A
authors.lastname: Assiri
authors.affiliation: Vétérinaires Sans Frontières Suisse, Nairobi, Kenya;
authors.forename: Ilona
authors.initials: I
authors.lastname: Gluecks
authors.affiliation: Ministry of Science and Communication, Khartoum, Sudan;
authors.forename: Bakri E
authors.initials: BE
authors.lastname: Musa
authors.affiliation: University of Bonn Medical Centre, 53127 Bonn, Germany;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meyer
authors.affiliation: University of Bonn Medical Centre, 53127 Bonn, Germany;
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Müller
authors.affiliation: Cairo University, 12613 Giza, Egypt;
authors.forename: Mosaad
authors.initials: M
authors.lastname: Hilali
authors.affiliation: National Veterinary Institute, 75189 Uppsala, Sweden;
authors.forename: Set
authors.initials: S
authors.lastname: Bornstein
authors.affiliation: Central Veterinary Research Laboratory, Dubai, United Arab Emirates;
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wernery
authors.affiliation: Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty Bern, University of Bern, 3012 Bern, Switzerland; Federal Department of Home Affairs, Institute of Virology and Immunology, Bern and Mittelhausern, Switzerland;
authors.forename: Volker
authors.initials: V
authors.lastname: Thiel
authors.affiliation: International Livestock Research Institute, Nairobi, Kenya; Institute of Veterinary Bacteriology, University of Bern, 3001 Bern, Switzerland.
authors.forename: Joerg
authors.initials: J
authors.lastname: Jores
authors.affiliation: University of Bonn Medical Centre, 53127 Bonn, Germany; German Centre for Infection Research, partner site Bonn-Cologne, Germany; drexler@virology-bonn.de drosten@virology-bonn.de.
authors.forename: Jan Felix
authors.initials: JF
authors.lastname: Drexler
authors.affiliation: University of Bonn Medical Centre, 53127 Bonn, Germany; German Centre for Infection Research, partner site Bonn-Cologne, Germany; drexler@virology-bonn.de drosten@virology-bonn.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
mesh_terms: D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D002162:Camelus / Q000821:virology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D017934:Coronavirus / Q000145:classification / Q000235:genetics / Q000502:physiology*; D018352:Coronavirus Infections / Q000453:epidemiology / Q000821:virology*; D019353:Endemic Diseases; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D065207:Middle East Respiratory Syndrome Coronavirus / Q000235:genetics / Q000502:physiology*; D010802:Phylogeny; D012529:Saudi Arabia / Q000453:epidemiology; D012689:Sequence Homology, Nucleic Acid; D014709:Vero Cells
keywords: coronavirus; ecology; evolution; livestock; zoonotic diseases