The researchers then asked, "What is it about these genes? Are they active genes, or is it something else about being a gene that's good?" Using another new technology, gene chips that help screen for products made by active genes, the researchers found that the genes that were targeted were disproportionately active ones.
In fact, Bushman said, the genes that are targeted are specifically ones that are turned on by infection with HIV itself. When the virus enters a cell, it triggers a response by the cell that includes making new proteins in response to the infection. So in essence, the HIV virus wields a double-edged sword, creating a weakness and then taking advantage of it.
Most HIV-infected cells die relatively quickly, within a day or two, Bushman said, so it's to the virus's advantage to be able to reproduce quickly. "Viruses that integrate into different points of the human genome inside a cell replicate with very different efficiencies," Bushman said. "There are bad places to be, where it's hard to express your genome, and there are other places where you can express very efficiently." HIV, it appears, is extremely efficient.
HIV differs from other types of genomic pathogens, Bushman said, that have evolved to live with their host on a long-term basis. These may target relatively benign regions of the genome where they don't hurt the host, and they reproduce because the cells continue to live, grow and divide, reproducing the pathogen as the cell itself reproduces.
"Not so with HIV," Bushman said. "HIV has aggressive targeting. That targeting is damaging to the host, but for an aggressive parasite in a cell that's only going to live for a day or so, it makes a sensible evolutionary strategy."
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Contact: Kristin Bertell
bertell@salk.edu
858-558-8552
Salk Institute
22-Aug-2002