Rhinovirus receptor found: colds carry on.

Rhinovirus receptor found; colds carry on

Researchers last week reported identifying and cloning the molecular receptor that enables rhinoviruses to infect human nasal-passage cells. Because rhinoviruses cause roughly half the cases of common cold, the accomplishment was widely reported as a breakthrough toward finding a cure for that most unpopular illness.

The new findings, reported in the March 10 CELL, have indeed generated excitement among virologists. Along with another paper in the same issue, in which researchers report cloning the poliovirus receptor, the work practically doubles the number of well-characterized virus receptors. But while an improved understanding of viral infectivity is sure to follow, researchers insist that reports of the common cold's death have been greatly exaggerated.

Virologists have sought since 1986 to learn the details of the "major" rhinovirus receptor--the cell-membrane docking site to which the great majority of rhinoviruses bind. But beyond the receptor's size and general characteristics, researchers had learned precious little about the molecule's amino acid sequence or its primary function on healthy cells.

Working separately, cell biologists and immunologists over the same period investigated a class of cell-surface molecules called intercellular adhesion molecules, including one known as ICAM-1. Among other things, ICAM-1 appears to play a role in concentrating white blood cells during episodes of inflammation. Last week's big news, reported by two teams working from opposite directions, is that ICAM-1 and the major rhinovirus receptor are one and the same.

The identity was reported by Timothy A. Springer of the Harvard Medical School in Boston and his colleagues, working on ICAM-1, and Jeffrey M. Greve and his co-workers at Molecular Therapeutics, Inc., in West Haven, Conn., who had been investigating the rhinovirus receptor. Vincent R. Racaniello at Columbia University in New York City and his colleagues also reported cloning the cell receptor for poliovirus, a rhinovirus relative responsible for paralytic polio.

The unexpected identity of ICAM-1 as the major rhinovirus receptor makes sense, at least in retrospect, researchers say. In response to cellular secretions characteristic of inflammatory reactions, the number of ICAM-1 molecules on the surfaces of some mucosal cells increases many fold, to as many as 350 million per cell. Thus in "choosing" ICAM-1 as their route of cellular infection, rhinoviruses--which themselves initiate an inflammatory response--guarantee themselves many new docking sites once they wedge a foot in the cellular door. "This explains a lot about the epidemiology of the common cold," says Ann Palmenberg, a virologist at the University of Wisconsin, Madison.

As headline writers were quick to note, an understanding of rhinovirus receptors may someday lead to a nasal-spray drug to block rhinovirus binding and infection in people. But keeping those sites blocked will be far from simple, researchers say, in part because the nose clears most substances from its lining every 15 minutes. Moreover, at least seven other types of viruses with different binding sites also cause colds.

"The new and exciting thing about these receptors is not so much that it's going to cure the cold," Palmenberg says. Rather, the well-defined ICAM-1 now provides researchers with an invaluable tool for viral receptor research. Only the receptors for the AIDS virus, the Epstein-Barr virus and the influenza virus are as well characterized. The new research, she says, "has the implication that other cellular adhesion molecules may well be major receptors for other, much more pathogenic viruses. You're going to see a lot of virologists suddenly catching up on all the literature about adhesion molecules."