Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Feb 5;370(1661):20140035.
doi: 10.1098/rstb.2014.0035.

The role of cellular adhesion molecules in virus attachment and entry

David Bhella  1
Affiliations

The role of cellular adhesion molecules in virus attachment and entry

David Bhella. Philos Trans R Soc Lond B Biol Sci. .

Abstract

As obligate intracellular parasites, viruses must traverse the host-cell plasma membrane to initiate infection. This presents a formidable barrier, which they have evolved diverse strategies to overcome. Common to all entry pathways, however, is a mechanism of specific attachment to cell-surface macromolecules or 'receptors'. Receptor usage frequently defines viral tropism, and consequently, the evolutionary changes in receptor specificity can lead to emergence of new strains exhibiting altered pathogenicity or host range. Several classes of molecules are exploited as receptors by diverse groups of viruses, including, for example, sialic acid moieties and integrins. In particular, many cell-adhesion molecules that belong to the immunoglobulin-like superfamily of proteins (IgSF CAMs) have been identified as viral receptors. Structural analysis of the interactions between viruses and IgSF CAM receptors has not shown binding to specific features, implying that the Ig-like fold may not be key. Both proteinaceous and enveloped viruses exploit these proteins, however, suggesting convergent evolution of this trait. Their use is surprising given the usually occluded position of CAMs on the cell surface, such as at tight junctions. Nonetheless, the reason for their widespread involvement in virus entry most probably originates in their functional rather than structural characteristics.

Keywords: cell adhesion; cell entry; cryo-electron microscopy; receptor; virus.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
The immunoglobulin superfamily of proteins are characterized as having domains of between seven and nine beta-strands arranged in two antiparallel sheets that form a sandwich structure, stabilized by a conserved disulfide bridge (a; rainbow coloured from the N-terminus (blue) to the C-terminus (red)). The crystal structure of a typical IgSF CAM—human JAM-A (b; PDB 1NBQ [34]) reveals that the two-domain molecule exists as a dimer in solution that is thought to represent the native structure at tight junctions (c). The ribbon diagrams are rainbow coloured across two domains, hence the colours of individual strands in (b) and (c) do not correspond to those in (a). Caliciviruses such as feline calicivirus (FCV) are RNA containing viruses that have a T = 3 icosahedral capsid (d; PDB 3M8L) [35]. This is composed of 180 capsid proteins (VP1) arranged as two classes of dimer: AB dimers (light and mid-blue) and CC dimers (dark blue). Cryo-electron microscopy of FCV (e) decorated with a soluble fragment of feline JAM-A (f) reveals that the receptor binds to the tip of the protruding domain of VP1. Receptor engagement induces conformational changes in the viral capsid such that the AB dimer rotates 15° anticlockwise and the CC dimer tilts away from the twofold symmetry axis (g; arrows). Docking high-resolution coordinates to the three-dimensional reconstruction led to the calculation of a quasi-atomic resolution map of the virus—receptor complex (h; FCV coloured blue, fJAM-A coloured magenta) that allowed the identification of putative contact residues (i). The VP1 AB dimer is viewed from the virus exterior, fJAM molecules viewed as if peeled away from the capsid surface and rotated 180o [36]. Panels (d–i) are presented as wall-eyed stereo pairs. (e–i) adapted from [36].
Figure 2.
Figure 2.
Picornaviruses are small proteinaceous icosahedral viruses, many of which have pronounced star-shaped mesas at their fivefold symmetry axes (a; arrow) that are surrounded by canyons which contains the receptor-binding sites for IgSF CAMs. Coxsackie B virus type 3 binds to the coxsackievirus and adenovirus receptor (b; CAR domain 1 only is shown, figure generated using PDB 1COV, 1KAC based on 1JEW [–44]). Coxsackie A virus type 21 binds to intercellular adhesion molecule 1 (ICAM-1) (c; PDB 1Z7Z [45]). Both molecules are oriented perpendicular to the capsid surface. A close up view of the interaction (receptors shown as ribbon diagrams) shows that CAR (d) and ICAM-1 (e) bind to the canyon in a similar but not identical orientation (fivefold symmetry axis indicated by a blue pentagon). (a–c) Stereoscopic views in which virus is radially coloured blue-white and receptor is radially coloured magenta-white. Panels (d) and (e) are monoscopic and the virus surface is shown in grey; the receptor is shown as a rainbow-coloured ribbon diagram.
Figure 3.
Figure 3.
(a,b) Views of the interaction between JAM-A (rainbow coloured) and the reovirus attachment protein σ-1 (magenta; wall-eyed stereo pairs—PDB 3EOY, 1NBQ [34,49]).
Figure 4.
Figure 4.
Evolution of virus–receptor interactions. Coxsackie B virus type 3 (CVB3) binds to the complement control protein decay-accelerating factor (DAF or CD55) at the apical cell surface prior to trafficking to tight junctions where entry is mediated by the coxsackievirus and adenovirus receptor (CAR). Comparison of the CVB3–DAF interaction (a; PDB 1COV, 3J24 [50]) with that of the distantly related picornavirus echovirus type 12 (EV12) (b; PDB 2C8I [51]) shows a markedly different receptor orientation. The structure is more easily interpreted when only a single DAF molecule is shown. CVB3 (c) binds primarily to domain 2 of DAF. EV12 binds predominantly domain 3 (d); moreover, there is approximately 90° rotation in the orientation of the two molecules on the capsid surface. These two viruses have quite different receptor interactions but have probably evolved from a common DAF-binding picornavirus ancestor. In each panel, the virus is radially coloured blue-white; DAF-CD55 is radially coloured magenta-white.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Matlin KS, Reggio H, Helenius A, Simons K. 1981. Infectious entry pathway of influenza virus in a canine kidney cell line. J. Cell Biol. 91, 601–613. (10.1083/jcb.91.3.601) - DOI - PMC - PubMed
    1. Yoshimura A, Ohnishi S. 1984. Uncoating of influenza virus in endosomes. J. Virol. 51, 497–504. - PMC - PubMed
    1. Prchla E, Plank C, Wagner E, Blaas D, Fuchs R. 1995. Virus-mediated release of endosomal content in vitro: different behavior of adenovirus and rhinovirus serotype 2. J. Cell Biol. 131, 111–123. (10.1083/jcb.131.1.111) - DOI - PMC - PubMed
    1. Wiethoff CM, Wodrich H, Gerace L, Nemerow GR. 2005. Adenovirus protein VI mediates membrane disruption following capsid disassembly. J. Virol. 79, 1992–2000. (10.1128/JVI.79.4.1992-2000.2005) - DOI - PMC - PubMed
    1. Rogers GN, Paulson JC. 1983. Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127, 361–373. (10.1016/0042-6822(83)90150-2) - DOI - PubMed

Substances

LinkOut - more resources