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Flu Virus Nipped in the Bud

24 March 1997 8:00 pm
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For many viruses, infiltrating a cell and replicating is only half the battle. Copies of the virus must then escape to infect other cells. Some viruses explode out of a host cell, destroying it; others, like the influenza virus, take a gentler path. Now a report in the latest EMBO Journal shows how the flu virus slips the confines of its cell--and how, by knocking out parts of two key viral genes, it may be held prisoner.

After the flu virus invades a cell, it commandeers the cell's genetic machinery to churn out viral RNA. Viral proteins assemble new viral particles that migrate to the cell wall, where they wrap themselves in the membrane. The bud, as it's called, pinches off and slips away. "It's almost like blowing bubbles," says Robert Lamb, a virologist at Northwestern University.

The virus's escape tools have been thought to be two proteins, hemagglutinin and neuraminidase, that jab like grappling hooks into the cell membrane, leaving "tails" dangling for the viral particles to grab onto. To test the importance of these "spike" proteins to the virus's Houdini act, Lamb and his colleagues performed a simple experiment: They disabled one, then both, of the portions of the flu virus's genes coding for the protein tails. Viruses able to manufacture just one complete spike protein had a slightly harder time forming buds in cultured cells. But the effect on viruses lacking both protein tails was stunning: The number of viral particles escaping from each cell dropped by 90%, and those escapees were severely deformed. Instead of balloons, Lamb says, they looked like a "string of sausages with great bulges coming out of the side--like something out of science fiction."

The deformed viruses, not surprisingly, had a much harder time infecting new cells than did their spherical brethren. That could make the tails of spike proteins a tempting target for new drugs, says virologist John Rose of the Yale University School of Medicine, who calls the research "an important piece of work."

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