Carcinoembryonic antigen-related cell adhesion molecule 5 is an important surface attachment factor that facilitates entry of middle east respiratory syndrome coronavirus

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

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9114-9127
Number of pages14
JournalJournal of Virology
Volume90
Issue number20
DOIs
Publication statusPublished - 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016, American Society for Microbiology.

ASJC Scopus Subject Areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this