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Entry of viruses through the epithelial barrier: pathogenic trickery

Nature Reviews Molecular Cell Biology volume 4, pages 57–68 (2003)Cite this article

Key Points

  • Mucosal surfaces — such as the lining of the gut or the reproductive tract — are the main point of entry for viruses into the body.

  • Almost all viruses interact with epithelial cells, and make use of the normal epithelial signalling and trafficking pathways of the host cell.

  • In addition to protein receptors, carbohydrate chains of proteoglycans and epithelial membrane glycosphingolipids have emerged as a new class of receptors for viral attachment to the host cell.

  • Viruses have also developed soluble virulence factors, which interact with epithelial cells independently of the virus and participate in the development of the virally induced pathology.

Abstract

Mucosal surfaces — such as the lining of the gut or the reproductive tract — are the main point of entry for viruses into the body. As such, almost all viruses interact with epithelial cells, and make use of the normal epithelial signalling and trafficking pathways of the host cell. In addition to protein receptors, carbohydrate chains of proteoglycans and epithelial-membrane glycosphingolipids have emerged as a new class of receptors for viral attachment to the host cell.

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Figure 1: Proteoglycans and glycosphingolipids.
Figure 2: Entry of HIV into a polarized epithelial cell by transcytosis.
Figure 3: The physio-pathology of diarrhoea induced by rotavirus.

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Acknowledgements

We apologize to our colleagues for omitting references in this review because of space limitations. We thank B. Wecksler and V. David for their editing of this manuscript. This work was supported by Agence Nationale de Recherche sur le Sida (ANRS) and SIDACTION/Ensemble Contre le SIDA funds to M.B.

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Authors and Affiliations

  1. Département de Biologie Cellulaire, Laboratory of Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Centre National de la Recherche Scientifique, INSERM, Université René Descartes, 22 rue Mechain, Paris, 75014, France

    Morgane Bomsel & Annette Alfsen

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  1. Morgane Bomsel
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  2. Annette Alfsen
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Correspondence to Morgane Bomsel.

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DATABASES

Entrez

haemagglutinin

neuraminidase

gB

gC

gD

gH

gL

Swiss-Prot

CAR

caveolin 1

CD13

CD46

DAF

ICAM1

integrin-αv

integrin-β6

JAM

LMP1

moesin

nectin 1

Glossary

PROTEOGLYCAN

An acidic macromolecule that is composed of glycosaminoglycan chains attached covalently to a protein core. Proteoglycans are found in the extracellular matrix, cell surfaces, and intracellular vesicles.

'RAFT' MEMBRANE MICRODOMAIN

A dynamic assembly of cholesterol and sphingolipids in the plasma membrane that is probably involved in cell signalling.

GLYCOSPHINGOLIPIDS

A highly polymorphic class of lipids with a common hydrophobic backbone — ceramide — that are composed of a fatty-acid chain linked to the sphingosine base and a hydrophilic oligosaccharide residue that protrudes into the extracellular space.

LECTIN

A cell-agglutinating protein of non-immune origin, which binds carbohydrates without modifying them.

TRANSCYTOSIS

A rapid and selective vesicular transcellular pathway that is characteristic of polarized epithelia. Cargo is transported from one pole of the cell to the opposite pole. The cargo remains enclosed in transcytotic vesicles, which precludes access to the cytosol and therefore viral infection of epithelial cells.

POLY-IMMUNOGLOBULIN RECEPTOR

This receptor is expressed at the basolateral surface of epithelial cells, allowing specific transcytosis towards the apical pole of mucosal dimeric IgA or pentameric IgM. At the apical pole, after cleavage of the extracellular region of the receptor, which is known as secretory component (SC), the mucosal IgA or IgM is released with SC as secretory IgA or IgM, and can act as the first defence against pathogens.

M CELL

'Membranous' or 'microfold' cell. This is a specialized epithelial cell covering the lymphoid Peyer's patches in the gut. M cells can internalize macromolecules and microorganisms and deliver them to the underlying lymphoid tissue.

ENDOSOME

A membranous transport vesicle that is involved in endocytosis.

TIGHT JUNCTION

A protein heterocomplex that connects neighbouring simple epithelial cells and controls the barrier function of the tight mucosal surface.

CLATHRIN-COATED VESICLE/PIT

An invagination of the plasma membrane that is surrounded by clathrin, a cytosolic protein that is formed by a triskelion of three heavy and three light chains. Triskelions assemble into a polyhedral lattice to form the clathrin coat.

MONONUCLEAR CELLS

Lymphocytes, dendritic cells and monocytes/macrophages. These are usually found in the blood, but also in tissues.

LAMINA PROPRIA

(chorion). This is formed of conjunctive tissue that is traversed by blood and lymphoid vessels. It supports epithelial cells through the basal membrane.

CAVEOLAE

Flask-shaped, cholesterol-rich invaginations of the plasma membrane that contain the protein caveolin. They might mediate the uptake of some extracellular material.

SIALYLOLIGOSACCHARIDE

An oligosaccharide chain that is linked to a terminal sialic acid (N-acetyl neuraminic acid).

GLYCOSAMINOGLYCAN

The polysaccharide moiety of proteoglycans, which is added posttranslationally and is composed of repeating disaccharide units.

HEPARAN SULPHATE

One of the glycosaminoglycan parts of proteoglycans, this is a long, polyanionic carbohydrate chain that consists of a repeating disaccharide unit.

GLYCOSYNAPSE

A membrane structure that provides a connection between two cells, and is involved in a glycosylation-dependent cell-adhesion/recognition processes.

ENTEROCYTE

An intestinal epithelial cell that is organized in monostratified layers.

PRIMARY CELL

A cell that is isolated directly from living tissues instead of transformed cells.

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Bomsel, M., Alfsen, A. Entry of viruses through the epithelial barrier: pathogenic trickery. Nat Rev Mol Cell Biol 4, 57–68 (2003). https://doi.org/10.1038/nrm1005

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