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The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza a Virus.

Rahman, Shah Kamranur
; 
Ansari, Mairaj Ahmed
; 
Gaur, Pratibha
; 
Ahmad, Imtiyaz
; 
Chakravarty, Chandrani
; 
Verma, Dileep Kumar
; 
Sharma, Anshika
; 
Chhibber, Sanjay
; 
Nehal, Naila
; ... show 1 more
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Issue Date
2021-04-21
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Abstract
To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoproteins as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein, binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found that CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (Carcinoembryonic cell adhesion molecule 6 or CEACAM6) as a glycoprotein receptor for Influenza A virus.
Citation
Viruses. 2021 Apr 21;13(5):726. doi: 10.3390/v13050726.
Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
Publisher
MDPI
Journal
Viruses
URI
http://hdl.handle.net/10033/622873
DOI
10.3390/v13050726
PubMed ID
33919410
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Article
Language
en
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1999-4915
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Attribution 4.0 International
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publications of the research group modell systems for infections and immunity (MSYS)