sealPurdue News

February 2000

Study reveals family secret of how viruses enter cells

WEST LAFAYETTE, Ind. – Like sleuths on the trail of a family of thieves, scientists have caught another viral intruder in action, revealing how two related viruses use similar but distinct strategies to enter cells.

A research group from Purdue University and State University of New York at Stony Brook has analyzed in molecular detail how the poliovirus interacts with a cell to gain entry. The group then compared the virus' tactics to those of human rhinoviruses, common cold viruses that are similar in size and structure to polioviruses. Both viruses belong to a family called picornaviruses.

Though these two sorts of viruses use different receptors to enter a cell, the scientists found that the receptors have a similar "footprint" and interact with the virus at similar sites on the virus shell, says Michael Rossmann, who is the Hanley Distinguished Professor of Biological Sciences at Purdue.

"Rhinoviruses and polioviruses each have shells that contain deep crevices or canyons, and this is the site at which binding occurs," Rossmann says. "In fact, this site may be a trigger for initiation of the subsequent uncoating step required for viral infection."

By comparing the processes used by rhinoviruses and polioviruses, scientists can for the first time describe in molecular detail the process by which a virus selectively attaches to its particular receptor. The findings also provide new insights on what differentiates one virus from another, and they may suggest ways for developing drugs that prevent illnesses caused by viral pathogens.

"Specificity is key to allowing the virus to enter a cell," Rossmann says. "A virus and its receptor must be perfect complements, like a lock and a key, in order for infection to occur."

Details of the study are in the Jan. 4 issue of the journal Proceedings of the National Academy of Sciences. Similar results were found by another team of researchers from the National Institutes of Health, Columbia University and Harvard Medical School, and they appear in the same issue of the journal.

Polioviruses cause poliomyelitis, a human disease that affects the central nervous system, injuring or destroying the nerve cells that control the muscles. Though effective vaccines have been developed against polioviruses, scientists did not have a clear understanding of how these viruses attached to molecules on the cell, called receptors, to initiate infection.

Using high-resolution cryo-electron microscopy and three-dimensional image reconstruction techniques, the scientists were able to obtain the first three-dimensional image of how poliovirus 1, one of the three types of polioviruses, binds to a receptor – a molecule called CD155 – on the cell.

CD155 is one of hundreds of types of receptors found on a cell, and each cell may contain thousands of these receptors on its membrane. Though cellular receptors are designed to carry out specific chemical processes for the cell, viruses have developed ways to use them for gaining entry into cells.

The CD155 receptor is made up of a single protein and is shaped somewhat like a leg divided into three sections, called domains, extending from a "hip" that penetrates the cellular membrane. Rossmann's group has determined that the virus attaches at a site on the receptor located at the "foot" end of the molecule.

They then compared the footprint to that of the ICAM-1 receptor, which is used by numerous rhinoviruses to infect cells, causing colds in humans. Rossmann's group became the first to construct a three-dimensional image of a human cold virus in 1986, and it since has analyzed the structures of several cold viruses attached to ICAM molecules.

"Though the CD155 receptor is similar in structure to the ICAM receptor, and binds to a similar site in the virus' canyon, there are distinct differences in the way in which the receptors bind and align themselves to these viruses," Rossmann says.

For example, the long, slender CD155 receptor binds by jutting its end into the canyon with part of the receptor lying roughly on the surface of the virus. The ICAM receptor, on the other hand, binds and radiates outward from the virus, Rossmann says.

In addition, the two receptors also contain different "residues" – carbohydrate units stuck on the outside of the receptor – that may allow the viruses to recognize their companion receptors.

"These viruses have evolved to recognize molecules on the cell receptor that just fit them, and we can now see the reason for that," he says.

The study also shows that as the receptors lock into their specific binding sites, the viruses bind with the receptor to form a single complex. This step may trigger the process that causes structural changes in the virus necessary for cell entry, Rossmann says.

The research was funded by the National Institutes of Health, the National Science Foundation and Purdue.

The research was the result of collaborations between the Purdue research groups of Tim Baker, an expert in electron microscopy; Richard Kuhn, an expert in virology and molecular biology; and Rossmann's group, plus Eckard Wimmer's team at the State University of New York, Stony Brook. Also, a number of postdoctoral fellows and graduate students from each laboratory participated in the work, including Yongning He, Valerie Bowman and Steffen Mueller.

Source: Michael Rossmann, (765) 494-4911,

Writer: Susan Gaidos, (765) 494-2081;

Purdue News Service: (765) 494-2096;

Related Web site:
Structural studies at Purdue



Interaction of the Poliovirus Receptor with Poliovirus

Yongning He, Valorie Bowman, Steffen Mueller, Carol Bator, Jordi Bella, Xiaozhong Peng, Timothy S. Baker, Eckard Wimmer, Richard J. Kuhn, and Michael G. Rossmann

The structure of the extracellular, three-domain, poliovirus receptor (CD155) complexed with poliovirus 1 (Mahoney strain) has been determined to 22 angstrom resolution by means of cryo-electron microscopy and three-dimensional image reconstruction techniques. Density corresponding to the receptor was isolated in a difference electron density map and fitted with known structures, homologous to those of the three individual CD155 immunoglobulin-like domains. The fit was confirmed by the location of carbohydrate moieties in the CD155 glycoprotein, by the conserved properties of elbow angles in the structures of cell surface molecules with immunoglobulin-like folds, and by the concordance with prior results of CD155 and poliovirus mutagenesis. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 (ICAM-1) receptor on human rhinoviruses. However, the orientation of the long, slender CD155 molecule relative to the poliovirus surface is quite different from the orientation of ICAM-1 on rhinovirus. In addition, the residues that provide specificity of recognition differ for the two receptors. The principal feature of receptor binding common to these two picornaviruses is the site in the canyon at which binding occurs. This site may be a trigger for initiation of the subsequent uncoating step required for viral infection.

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