Findings have implications for better-designed gene therapies
LEDGF, a human DNA-associated protein, is the first example of a cellular protein controlling the location of HIV integration in human cells. The red cylinder is an HIV integration complex. The green box is LEDGF, acting as a tether by binding to both HIV integrase and a cellular chromosome. (Credit: Frederic Bushman, PhD, University of Pennsylvania School of Medicine)
A human DNA-associated protein called LEDGF is the first such molecule found to control the location of HIV integration in human cells, according to a new study from researchers at the University of Pennsylvania School of Medicine. This study, published in this weeks early online edition of Nature Medicine, describes the first clear target for modulating where viruses insert into the human genome, which has implications for better design of gene-therapy delivery. Retroviral vectors are often used to introduce therapeutic genetic sequences into human chromosomes, such as in the delivery of Factor VIII for hemophilia patients.
HIV integrates into active transcription units on chromosomes within the nucleus of human cells. These units are sites that lead to efficient expression of the viral genome. Most HIV-infected cells in a patient will have a very short life span, a day or less. "We surmise that this strategy helps the virus make hay while the sun is shining, as it were, producing lots of viral copies during a short time, so that the virus can maximize production of daughter virions," says Frederic Bushman, PhD, Professor of Microbiology at Penn.
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