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Viral close-up: in from the cold.

The enemy might not yet be ours, but now we know what it looks like: Scientists have generated the first three-dimensional, atomic-scale model of a cold virus. The virus's structure makes development of a conventional vaccine unlikely, says research head Michael G. Rossmann of Purdue University in West Lafayette, Ind., but it does suggest other ways to prevent colds.

The collaborative effort between scientists at Purdue and the University of Wisconsin in Madison was reported in the Sept. 12 NATURE. It is the first three-dimensional description of a virus that infects animals.

The virus depicted, one of more than 80 members of the cold virus family, looks like a 20-sided soccer ball; within the ball is an RNA core. Each triangular face is made of protein and has hills and a valley. Within each valley, Rossmann believes, is the apparatus with which the virus grabs on to a host cell; the ridges are the sites recognized by the host's immune system.

This shape makes the cold virus a survivor and is a major roadblock to a vaccine. The constantly exposed ridges are constantly changing, allowing viral descendants to sneak unrecognized past an immune system primed to recognize previous versions of the virus. And antibodies can't fit into the valleys in which the stable receptors reside.

But the fight is far from lost. "We might be able to do something with the [host cell] receptor," says Rossmann. "The virus has to be able to infect the host." If something can be found to cover the host cell receptor, he suggests, infection could be prevented.

In a commentary in the same issue of NATURE, Don C. Wiley of Harvard University cites the viral description as "a tour de force of modern X-ray crystallography." It is, he notes, "certainly nothing to sneeze at."

Wiley suggests three approaches to a cold preventive. Like Rossmann, he proposes blocking the host cell receptor; his other suggestions concern the virus's protein coat. The virus has to get undressed--lose its shell -- to enter the cell, and understanding the structural changes involved may suggest a way to block the disrobing, he says. In order to leave a cell following replication and infect another cell, the virus has to assemble a new coat; a better understanding of this process could provide information necessary to keep viruses from getting dressed.

The researchers marshaled Purdue's Cyber 205 supercomputer and Cornell University's high-energy synchrotron in their attack on the virus. They hit crystallized cold viruses (SN:3/12/83, p. 165) with X-rays from the synchrotron and studied the diffraction patterns with the computer; the resulting map has a margin of error of about one-half angstrom. Approximately 6 million pieces of data were considered. Doing the calculations without a supercomputer could have taken 10 years instead of a month, Rossmann estimates. He says the same procedure could be used to study the AIDS virus, provided it can be crystallized.

The structure, the researchers note, is remarkably similar to those of previously described plant viruses and suggests a common evolutionary history.
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Author:Silberner, Joanne
Publication:Science News
Date:Sep 21, 1985
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