Purdue University scientists said yesterday that they have determined the complete, three-dimensional architecture of a common cold virus, including the position of every atom. The feat promises to shed new light on how one of the world's most common viruses attacks the body.
Although officials of the National Science Foundation, which sponsored part of the research, billed the step as possibly leading to development of a vaccine against colds, the research team's leader said he thought it would never be possible to make such a vaccine.
On the other hand, the findings do suggest that a new antiviral drug might be designed to treat colds. This is the first time scientists have learned the detailed structure of any virus infecting animals.
Biologists have long known the general shape of the cold virus, which can be seen in fuzzy outlines under an electron microscope. It looks something like a microscopic soccer ball, its outer wall composed of 20 triangles that fit together to make the geometric shape known as an icosahedron.
Inside this hollow shell, made of protein, is a small amount of genetic material which, when released inside a human cell, commandeers the cell's apparatus, directing it to make many identical copies of the virus. Viruses are nonliving objects that can reproduce only by such a cell seizure.. The new findings add a view of the exact positions of individual atoms that make up protein molecules. They show that each triangle of the protein shell has peaks and valleys formed by the irregular shape of protein molecules making up the shell.
Michael G. Rossmann, who led the Purdue team, said Roland Rueckert at the University of Wisconsin had used the newly determined structure to find that the part of the shell that must attach to a cell to cause infection lies deep within a "canyon" on each of the 20 triangular sides.
The site appears too narrow for the body's infection-fighting antibodies to get in and block infection.
Still, the finding raises the possibility that a synthetic molecule could be designed small enough to enter the canyon and bind to the attachment site, preventing infection. Such a molecule could be the basis of a new kind of antiviral drug.
Vaccines against cold viruses have long been considered virtually hopeless because at least 100 different kinds of viruses cause colds and each would require its own vaccine. The virus on which Rossmann worked is only one of these, known as human rhinovirus 14.
Each time a person has a cold, his immune system must tailor new antibodies capable of attacking that particular virus. This takes a few days, during which the virus spreads, causing disease.
When enough antibodies form, however, they stop the spread and leave the person immune to that type of virus but vulnerable to others causing similar symptoms.
Antibodies that eventually stop a cold infection bind to sites on the canyon rim and probably distort the canyon's shape so it no longer can attach to a human cell. These rim sites, however, are different in each type of cold virus.
To determine the virus structure, researchers crystallized the viruses and X-rayed them at Cornell University's High Energy Synchrotron Source.
The information from thousands of such pictures was then fed into Purdue's supercomputer which, after a month of data processing, produced a composite image, showing where each atom was situated in three dimensions.