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

• Published in: PloS one Vol. 9; no. 11; p. e112060
• Main Authors: Caì, Yíngyún, Yú, Shu Qìng, Postnikova, Elena N, Mazur, Steven, Bernbaum, John G, Burk, Robin, Zhāng, Téngfēi, Radoshitzky, Sheli R, Müller, Marcel A, Jordan, Ingo, Bollinger, Laura, Hensley, Lisa E, Jahrling, Peter B, Kuhn, Jens H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.11.2014; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - immunology; Bats; Biology and life sciences; Biotechnology; Cell Line; Cell lines; Cell surface; Chiroptera; Chiroptera - virology; Chlorocebus aethiops; Coronaviridae; Coronavirus Infections - transmission; Coronavirus Infections - virology; Coronaviruses; Dipeptidyl Peptidase 4 - metabolism; Dipeptidyl-peptidase IV; Disease Reservoirs - virology; Disease Susceptibility; Divergence; Electron microscopy; Etiology; Genomes; Humans; Hypotheses; Immunofluorescence; Infections; Infectious diseases; Influenza; Laboratories; Medicine and Health Sciences; Middle East Respiratory Syndrome Coronavirus - pathogenicity; Middle East Respiratory Syndrome Coronavirus - physiology; Persistent infection; Receptors, Virus - metabolism; Reservoirs; Respiratory diseases; RNA polymerase; Transmission electron microscopy; Tylonycteris; Vero Cells; Viral infections; Viral Tropism; Viruses; Middle East; United States > US; Maryland; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112060

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.