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.
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 dromedarie...
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doaj-7f52b184f1244d619c5045dcfc1e7e4b2020-11-25T02:16:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11206010.1371/journal.pone.0112060CD26/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.Yíngyún CaìShu Qìng YúElena N PostnikovaSteven MazurJohn G BernbaumRobin BurkTéngfēi ZhāngSheli R RadoshitzkyMarcel A MüllerIngo JordanLaura BollingerLisa E HensleyPeter B JahrlingJens H KuhnMiddle 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.http://europepmc.org/articles/PMC4237331?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yíngyún Caì Shu Qìng Yú Elena N Postnikova Steven Mazur John G Bernbaum Robin Burk Téngfēi Zhāng Sheli R Radoshitzky Marcel A Müller Ingo Jordan Laura Bollinger Lisa E Hensley Peter B Jahrling Jens H Kuhn |
spellingShingle |
Yíngyún Caì Shu Qìng Yú Elena N Postnikova Steven Mazur John G Bernbaum Robin Burk Téngfēi Zhāng Sheli R Radoshitzky Marcel A Müller Ingo Jordan Laura Bollinger Lisa E Hensley Peter B Jahrling Jens H Kuhn 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 |
author_facet |
Yíngyún Caì Shu Qìng Yú Elena N Postnikova Steven Mazur John G Bernbaum Robin Burk Téngfēi Zhāng Sheli R Radoshitzky Marcel A Müller Ingo Jordan Laura Bollinger Lisa E Hensley Peter B Jahrling Jens H Kuhn |
author_sort |
Yíngyún Caì |
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. |
title_short |
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. |
title_full |
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. |
title_fullStr |
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. |
title_full_unstemmed |
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. |
title_sort |
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. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4237331?pdf=render |
work_keys_str_mv |
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