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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.
PLoS One. 2014; 9(11):e112060.Plos

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+Show Affiliations

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.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.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.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.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.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.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.United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.ProBioGen AG, Berlin, Germany.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.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.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25409519

Citation

Caì, Yíngyún, et al. "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." PloS One, vol. 9, no. 11, 2014, pp. e112060.
Caì Y, Yú SQ, Postnikova EN, et al. 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. PLoS One. 2014;9(11):e112060.
Caì, Y., Yú, S. Q., Postnikova, E. N., Mazur, S., Bernbaum, J. G., Burk, R., Zhāng, T., Radoshitzky, S. R., Müller, M. A., Jordan, I., Bollinger, L., Hensley, L. E., Jahrling, P. B., & Kuhn, J. H. (2014). 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. PloS One, 9(11), e112060. https://doi.org/10.1371/journal.pone.0112060
Caì Y, et al. 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. PLoS One. 2014;9(11):e112060. PubMed PMID: 25409519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Caì,Yíngyún, AU - Yú,Shu Qìng, AU - Postnikova,Elena N, AU - Mazur,Steven, AU - Bernbaum,John G, AU - Burk,Robin, AU - Zhāng,Téngfēi, AU - Radoshitzky,Sheli R, AU - Müller,Marcel A, AU - Jordan,Ingo, AU - Bollinger,Laura, AU - Hensley,Lisa E, AU - Jahrling,Peter B, AU - Kuhn,Jens H, Y1 - 2014/11/19/ PY - 2014/06/30/received PY - 2014/10/12/accepted PY - 2014/11/20/entrez PY - 2014/11/20/pubmed PY - 2015/7/15/medline SP - e112060 EP - e112060 JF - PloS one JO - PLoS One VL - 9 IS - 11 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25409519/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_ L2 - https://dx.plos.org/10.1371/journal.pone.0112060 DB - PRIME DP - Unbound Medicine ER -