title: CD26/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection.
abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Yíngyún
authors.initials: Y
authors.lastname: Caì
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Shu Qìng
authors.initials: SQ
authors.lastname: Yú
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Postnikova
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Mazur
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: John G
authors.initials: JG
authors.lastname: Bernbaum
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Robin
authors.initials: R
authors.lastname: Burk
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Téngfēi
authors.initials: T
authors.lastname: Zhāng
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Sheli R
authors.initials: SR
authors.lastname: Radoshitzky
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Müller
authors.affiliation: ProBioGen AG, Berlin, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Jordan
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Bollinger
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002460:Cell Line; D002685:Chiroptera / Q000821:virology*; D002522:Chlorocebus aethiops; D018352:Coronavirus Infections / Q000635:transmission / Q000821:virology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004197:Disease Reservoirs / Q000821:virology; D004198:Disease Susceptibility; D006801:Humans; D065207:Middle East Respiratory Syndrome Coronavirus / Q000472:pathogenicity / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism; D014709:Vero Cells; D056189:Viral Tropism
chemical_list: D000911:Antibodies, Monoclonal; D011991:Receptors, Virus; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4