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10.3390/v13050726
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Article

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

by
Shah Kamranur Rahman
1,2,*,
Mairaj Ahmed Ansari
3,†,
Pratibha Gaur
4,
Imtiyaz Ahmad
1,
Chandrani Chakravarty
1,
Dileep Kumar Verma
1,
Anshika Sharma
5,
Sanjay Chhibber
6,
Naila Nehal
7,
Dagmar Wirth
4 and
Sunil K. Lal
1,5,*
1
Virology Group, International Centre for Genetic Engineering & Biotechnology, New Delhi 110067, India
2
Department of Infection Biology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK
3
H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA
4
Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
5
School of Science, Monash University, Bandar Sunway 47500, Selangor DE, Malaysia
6
Microbiology Department, Panjab University, Chandigarh 160014, India
7
Career Institute of Medical & Dental Sciences and Hospital, Lucknow 226020, India
*
Authors to whom correspondence should be addressed.
†
Present address: Host Pathogen Interaction Laboratory, Department of Biotechnology, SCLS, Jamia Hamdard, New Delhi 110062, India.
Viruses 2021, 13(5), 726; https://doi.org/10.3390/v13050726
Submission received: 1 April 2021 / Accepted: 10 April 2021 / Published: 21 April 2021
(This article belongs to the Special Issue Molecular Determinants of Enveloped Virus Assembly)
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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.
Keywords: virus; lipid raft; flu; influenza A Virus; receptor; neuraminidase; hemagglutinin; carcinoembryonic antigen (CEA); carcinoembryonic cell adhesion molecule (CEACAM); CEACAM6; CD66c; IgG super family; sialic acid virus; lipid raft; flu; influenza A Virus; receptor; neuraminidase; hemagglutinin; carcinoembryonic antigen (CEA); carcinoembryonic cell adhesion molecule (CEACAM); CEACAM6; CD66c; IgG super family; sialic acid
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MDPI and ACS Style

Rahman, S.K.; Ansari, M.A.; Gaur, P.; Ahmad, I.; Chakravarty, C.; Verma, D.K.; Sharma, A.; Chhibber, S.; Nehal, N.; Wirth, D.; et al. The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus. Viruses 2021, 13, 726. https://doi.org/10.3390/v13050726

AMA Style

Rahman SK, Ansari MA, Gaur P, Ahmad I, Chakravarty C, Verma DK, Sharma A, Chhibber S, Nehal N, Wirth D, et al. The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus. Viruses. 2021; 13(5):726. https://doi.org/10.3390/v13050726

Chicago/Turabian Style

Rahman, Shah Kamranur, Mairaj Ahmed Ansari, Pratibha Gaur, Imtiyaz Ahmad, Chandrani Chakravarty, Dileep Kumar Verma, Anshika Sharma, Sanjay Chhibber, Naila Nehal, Dagmar Wirth, and et al. 2021. "The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus" Viruses 13, no. 5: 726. https://doi.org/10.3390/v13050726

APA Style

Rahman, S. K., Ansari, M. A., Gaur, P., Ahmad, I., Chakravarty, C., Verma, D. K., Sharma, A., Chhibber, S., Nehal, N., Wirth, D., & Lal, S. K. (2021). The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus. Viruses, 13(5), 726. https://doi.org/10.3390/v13050726

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