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Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus.

Authors :
Che-Man Chan
Hin Chu
Yixin Wang
Bosco Ho-Yin Wong
Xiaoyu Zhao
Jie Zhou
Dong Yang
Sze Pui Leung
Jasper Fuk-Woo Chan
Man-Lung Yeung
Jinghua Yan
Guangwen Lu
George Fu Gao
Kwok-Yung Yuen
Source :
Journal of Virology. Oct2016, Vol. 90 Issue 20, p9114-9127. 14p.
Publication Year :
2016

Abstract

The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERSCoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022538X
Volume :
90
Issue :
20
Database :
Academic Search Index
Journal :
Journal of Virology
Publication Type :
Academic Journal
Accession number :
118557093
Full Text :
https://doi.org/10.1128/JVI.01133-16