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

Shah Rahman,Pratibha Gaur,Dileep Verma,Sanjay Chhibber,Sunil Lal,Chandrani Chakravarty,Dagmar Wirth,Imtiyaz Ahmad,Mairaj Ansari,Naila Nehal,Anshika Sharma

doi:10.3390/v13050726

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.

Highlights

The outermost surface of mammalian cells typically bears a covering of branched sugar residues that allow a wide range of interactions with different biomolecules of the matrix [1]
A549 lung cells transiently transfected with untagged CD66c gene showed a rise in the expression of this molecule at the host cell surface when monitored by flow cytometry (Figure 1a)
The results obtained from these experiments provided sufficient evidence that suggested CD66c as the glycoprotein receptor for influenza virus

Summary

Introduction

The outermost surface of mammalian cells typically bears a covering of branched sugar residues (oligosaccharides) that allow a wide range of interactions with different biomolecules (hormones, cytokines, growth factors, etc.) of the matrix [1]. These oligosaccharides are often linked to membrane proteins (glycoproteins) or lipid (gangliosides) at the cell surface. The type of sugar residues and their branching is responsible for deciding the specificity of oligosaccharides towards biomolecules coming in contact with the cell surface These interactions between oligosaccharides and biomolecules play a diverse physiological role and are important in maintaining communication and transport of molecules between the cell and its surroundings [2]. This less specific interaction of viruses with terminal SIA is followed by a more specific interaction of viral spike proteins with a subset of host glycoprotein receptors that effectively accompany the virus into cells and drive the ingested cargo to destined endocytic pathways or intracellular routings [5]

Methods

Results

Conclusion