DNA target' to block HIV found
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.
This is the first example of a cellular factor that`s a clear player in target site selection
Dr Frederic Bushman, professor of microbiology at the university
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."
http://news.bbc.co.uk/2/hi/health/4746926.stm
