http://news.bbc.co.uk/2/hi/health/4746926.stm

DNA target' to block HIV found

Last Updated: Sunday, 26 February 2006, 00:05 GMT

American scientists have discovered how a molecule controls HIV's
ability to hijack the genetic machinery of human cells.

The finding gives experts a new target for blocking the virus, according
to the journal Nature Medicine.

The molecule, called LEDGF, is a cellular protein that dictates where
HIV can integrate into a cell's DNA.

It could also point the way to safer gene therapy, says the University
of Pennsylvania School of Medicine team.

Gene therapy

Scientists have been looking at ways of treating diseases by introducing
a new gene into a cell.

The new gene may be used to replace a function that is missing because
of a defective gene.

However, there have been concerns about the possible risk of cancer
associated with such treatments in light of recent experiments where
integration of gene therapy carriers close to cancer genes contributed
to leukaemia in gene therapy patients.

Dr Frederic Bushman and colleagues believe that by increasing the
understanding of how gene sequences - that of HIV in their study -
insert into the human genome, this therapeutic process could be made
safer.

Stopping cell invasion

HIV is a retrovirus. The genetic material of retroviruses is called RNA.

To enter a human cell, the virus must convert RNA into the genetic
material of cells - DNA.

It does this using an enzyme called reverse transcriptase. Another
enzyme, called integrase, is needed in order for the DNA copy to add
itself into the cell's DNA, which is housed in rod-shaped structures
called chromosomes.

When the infected cell divides, the viral DNA will be copied and
inherited along with the rest of the cell's DNA.

Dr Bushman's team found that LEDGF binds to HIV integrase and specific
sites on the cell's chromosomes.

When they manufactured some cells that were depleted of LEDGF they found
that HIV integration was much less frequent, showing LEDGF was indeed
important for HIV to highjack the cell's genetic machinery.

"This implies that LEDGF is part of the machinery that helps dictate the
placement of retroviral integration sites within chromosomes," said Dr
Bushman.

"This is the first example of a cellular factor that's a clear player in
target site selection," he added.

Roger Pebody, treatment specialist at the Terrence Higgins Trust said:
"This is an interesting study, which gives us more information on how
the HIV virus works within the body.

"Scientists and researchers are constantly working to increase our
understanding of HIV. The more we understand, the easier it is to come
up with effective treatments."

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