Researchers glimpse polio virus as it enters...( Images could shed light on more int...)

Images could shed light on more intractable bugs

Boston, MAJanuary 20, 2000A team of researchers at Harvard Medical School and other institutions has produced the first 3-D structuresthe biological equivalent of snapshotsof the poliovirus in the moments after it attaches to and enters a host cell. The structures, which appear in the February Journal of Virology, follow on the heels of a molecular rendering by the same team of the virus as it attaches to the receptor of the host cell. The virusreceptor complex was published in the January 6 Proceedings of the National Academy of Sciences.

Though poliovirus has yielded to medical know-howvaccination programs have eradicated it from the Western world and promise to eliminate it globallyit has proved to be a stubborn subject for scientists. Surprisingly little is known about how poliovirus enters the cells of the intestines, let alone how it makes its way to the nervous system where it can damage motor neurons and cause paralysis. Some have suspected that after attaching to the host cell, the virus undergoes a series of conformational changes, producing two intermediate forms. James Hogle and colleagues at Harvard Medical School and the National Institutes of Health have determined the structure of these two intermediate forms using a powerful combination of methodscryoelectron microscopy and X-ray crystallography.

Hogle, who is professor of biological chemistry and molecular pharmacology, and his colleagues have interpreted the images, together with the receptorvirus structure, to tell a story of an extremely dynamic particle. From the moment it attaches to its host, the poliovirus appears to make tiny adjustments in its protein shell that allow it to grab onto its host receptor more tightly. Once bound, the virus creates temporary openings in its shell through which it throws out tiny protein threads which embed in the host cell membrane, not only anchoring the vir
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Contact: Peta Gillyatt
gillyatt@hms.harvard.edu
617-432-0443
Harvard Medical School
20-Jan-2000