- 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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