HIV Targets Specific Human
DNA To Attach To In Cell


NEW YORK (Reuters Health) - As HIV replicates within human cells, it latches on to specific DNA within the human genome. But rather than grabbing genes at random, new research suggests the virus selects those genes that will help it replicate in the quickest--and most lethal--way possible.
The "surprise" finding could someday help scientists design better gene-based therapies to fight HIV, the researchers add.
"Sites of HIV integration in the human genome are not randomly distributed but instead are enriched in active genes and regional hotspots," conclude researchers led by Dr. Frederic Bushman of The Salk Institute for Biological Science in San Diego, California. They report the finding in the current issue of the journal Cell.
HIV, like all retroviruses, reproduces itself by entering a cell, producing a copy of its own DNA, and then inserting that DNA into a chromosome of the host cell. As the host cell uses its genetic material to produce proteins and other gene products, it now also makes copies of the invader virus' genome.
Taking advantage of the recent complete mapping of the human genome, Bushman and his colleagues focused their research on one step in this process: determining which spots on the human genome HIV favors.
They found that, far from alighting willy-nilly onto human DNA, HIV homes in on highly active genetic "hotspots" that seem tailor-made to allow quick replication of the virus. These genes churn out proteins and other materials at relatively high rates compared to non-targeted genes, the researchers explain. Selecting these hotspots "makes a lot of biological sense if the targeting has evolved to promote efficient expression of the (HIV) genome once it integrates into the cell," Bushman said in a statement.
What's more, the researchers theorize that the very act of viral invasion may trigger a rise in activity in these target genes--thus enhancing their ability to replicate HIV. In other words, HIV "wields a double-edged sword, creating a weakness and then taking advantage of it," according to officials at The Salk Institute.
The findings could boost efforts to develop safe, effective gene therapies aimed at fighting HIV, the researchers add. They explain that by identifying specific genes targeted by HIV, scientists may make better choices when it comes to delivering gene therapy in as efficient and non-toxic a manner possible.
SOURCE: Cell 2002;110:521-529.
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