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Set a virus to catch a virus - Novel treatment may defend the immune system against the worst ravages of HIV

点击量:   时间:2017-11-19 06:01:08

By Nell Boyce GENE therapy could prevent HIV from wrecking the immune system, a unique study on identical twins suggests. Preliminary results from the trial, reported at the AAAS, indicate that such treatment might ward off the opportunistic infections that eventually kill people with AIDS. Richard Morgan of the National Institutes of Health near Washington DC has genetically modified a harmless retrovirus to carry genes that disrupt two proteins, called Tat and Rev, which HIV needs to reproduce. When the modified retrovirus enters CD4 cells, which are usually killed by HIV, it produces an altered form of Rev that interferes with the protein’s ability to move viral RNA from the cell’s nucleus into the cytoplasm. It also produces an “antisense” RNA sequence that stops Tat binding to a sequence of viral RNA. Tat and Rev vary little between HIV and SIV, the related virus that infects monkeys. So the first test Morgan tried was to take CD4 cells from three rhesus macaques, infect them with a similarly modified retrovirus, and return the cells to the monkeys’ bodies. The macaques were injected with SIV, and monitored for more than a year. Throughout the experiment, all three had much lower levels of SIV circulating in their blood than three monkeys which did not receive the retrovirus-infected cells. The test monkeys’ levels of CD4 cells also remained high, and their lymph nodes showed no signs of the damage normally caused by SIV, showing that the treatment had protected the animals from the virus’s worst ravages. “This was the first really good evidence in an animal model that perhaps these techniques could help humans,” says Morgan, who reports the results in this month’s Nature Medicine (vol 4, p 181). The results from the human trial are equally encouraging. In August 1996, Morgan and his colleagues Robert Walker, Clifford Lane and Michael Blaese persuaded eight pairs of identical twins to join their trial. One of each pair was HIV-positive. This gave each HIV patient a ready source of genetically identical CD4 cells that were free from HIV. The researchers took CD4 cells from each healthy twin and infected half the sample with the modified retrovirus carrying the therapeutic genes. The other half was exposed to a similar retrovirus carrying only a marker gene so the researchers could see how long the cells lasted. Then all the cells were transfused into the twin with HIV. Morgan and his colleagues took regular blood samples from the patients, recording the relative quantities of the two types of retrovirus-infected cells. The cells with the therapeutic genes clearly survived much better in seven out of the eight patients. After several months, there was a 20-fold difference in one case If the technique becomes generally accepted, Morgan says that a patient’s own cells would be used. “You can still do this technique in HIV-infected individuals,” he notes. But while Morgan’s retrovirus will ferry therapeutic genes into CD4 cells in the test tube, it won’t do so efficiently if simply injected into the bloodstream. Ultimately, Morgan would like to eliminate the laborious step of removing CD4 cells from the body and culturing them in the lab. This would mean using a genetically modified virus to seek out and infect CD4 cells in the body. One interesting possibility, Morgan says,