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Flu virus shows spring-loaded mechanism.

Viruses have evolved complex and cunning methods of infecting their preferred hosts. Now, researchers believe they have discovered a twist in viral cleverness -- a spring-loaded mechanism within the protective outer membrane of the influenza virus. This mechanism apparently helps the virus spill its DNA into cells, causing the misery known to millions as "the flu."

Spring-loading offers an explanation for how the virus brings out of hiding short bits of protein, called peptides. These peptides start a critical stage of infection known as membrane fusion, report structural biologists Chavela M. Carr and Peter S. Kim in the May 21 CELL. "We've provided a possible solution to a long-standing puzzle," says Kim, a Howard Hughes Medical Institute investigator at the Massachusetts Institute of Technology. Kim and Carr base their model on flu-membrane research they conducted at the Whitehead Institute for Biomedical Research in Cambridge, Mass.

During infection, Kim explains, a flu virus latches on to a cell, causing part of the cell's outer membrane to bulge inward, seal off, and break free. This encloses the virus in a free-floating bubble called an endosome. But to move to the next stage of infection, the virus must fuse with the endosome and spill its DNA into the cell.

To do this, certain peptides normally hidden within the viral membrane must be lifted above the surface. Special spring-loaded regions of the membrane, triggered by increased acidity within the endosome, accomplish this feat. Strands of amino acids in the viral membrane -- usually held under tension -- spring up, causing the peptides to make contact with the inside surface of the endosome. This connection kicks off membrane fusion.

Successful infection depends on membrane fusion, making it a prime target for antiviral drugs. "If you could prevent membrane fusion, I think there's no question you could prevent infection," says Kim.

The researchers have also found that the outer shell of HIV, the virus that causes AIDS, contains an amino-acid pattern strongly resembling that of the spring-loaded region of the influenza virus. The spring structure may thus prove critical in the life cycle of other kinds of viruses.
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Title Annotation:mechanism within outer virus membrane explains how influenza virus brings out peptides that start membrane fusion
Author:Pendick, Daniel
Publication:Science News
Article Type:Brief Article
Date:May 29, 1993
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