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HIV targets active genes in cells

LA JOLLA, CALIF. - HIV selectively inserts itself into active areas of a host cell's genome, Salk Institute researchers have found for the first time. The fact that the virus hooks itself up to areas of the cell's genome that are busy expressing themselves may help explain why HIV can replicate, or reproduce itself, so rapidly. The findings are being published as the cover article in the Friday, August 23, issue of the journal Cell.

"HIV seems to be targeting not just genes, but active genes," said Salk researcher Frederic Bushman, a specialist in infectious diseases who headed the research team. "That makes a lot of biological sense if the targeting has evolved to promote efficient expression of the viral genome once it integrates into the cell."

The findings may have implications for developing more effective gene therapies, said Bushman, Associate Professor in the Infectious Disease Laboratory. Gene therapy involves treating genetic disorders by using a mutated retrovirus to insert a new gene into a defective genome. Gene therapy could be made safer and more effective by knowing more about and taking advantage of a retrovirus's targeting specificity, he said.

Retroviruses like HIV reproduce themselves by infecting a cell, making a DNA copy of the virus's RNA genome, and integrating that DNA copy into a chromosome of the host. When the genome of the host is "read" to produce proteins and gene products, so is the genome of the virus-which reproduces itself. The question Bushman and his team sought to answer was, where in the human chromosome does the virus integrate itself?

The team took advantage of the recently published human genome sequence. The researchers infected human cells in tissue culture with the HIV virus, and then broke open the cells and sequenced pieces of DNA to find out where the viral DNA ended up. By matching DNA segments with the published human genome sequence, they found that that the viral DNA mostly ended up
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Contact: Kristin Bertell
bertell@salk.edu
858-558-8552
Salk Institute
22-Aug-2002


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