CHANGING just a single 鈥渓etter鈥� in one human gene makes cells resistant to HIV. The discovery might just lead to new ways to treat AIDS.
Rhesus monkeys are resistant to HIV infection, and last year a team in Boston showed that this resistance depends a gene called Trim5alpha. The exact mechanism is not understood, but Trim5alpha is thought to code for a protein that attacks several kinds of retroviruses, including HIV, after they enter a cell, preventing them replicating.
Humans have a different version of the Trim5alpha gene. It protects against several kinds of retroviruses, but not HIV. To find out why, a team led by Jonathan Stoye of the National Institute for Medical Research in London replaced parts of the human gene with the equivalent section of the rhesus gene.
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The recombined genes were added to cells, and their protective power was assessed by exposing the cells to various kinds of retroviruses. The results showed that one region of the gene is crucial for HIV resistance (Current Biology, vol 15, p 73). 鈥淲e were able to make the human protein active against HIV with a single amino acid change,鈥� Stoye says.
In theory, he says, it might be possible to treat infected people by removing some immune cells from each patient, adding the modified version of the gene and then reimplanting the cells. While the monkey version of the protein might be rejected as foreign by the immune system, there is far less risk of this with a slightly altered human version. 鈥淵ou want to use molecules as close to the human molecule as possible,鈥� says Joseph Sodroski of the Harvard School of Public Health, a member of the Boston team.
If the modified gene really does make cells resistant to HIV infection, the altered cells would help restore people鈥檚 immune systems, though the virus would remain in their bodies. But Sodroski thinks it is too soon to raise people鈥檚 hopes. 鈥淎ll this hinges on effective methods of gene therapy, which is still a big hurdle.鈥� Stoye is now planning to test the idea in mice. If this is successful, human trials could begin within a year.
