Gene fights off HIV
Extra copies generate protein that confers disease resistance.
A gene that partly explains people's different susceptibility to HIV has been identified by US scientists. The discovery may help doctors tailor treatment to patients' genetic make-up.
Researchers know that certain people are naturally resistant to HIV. Some people develop full-blown AIDS several months after infection by the virus, whereas others remain disease-free for decades.
Differences in a gene called CCL3L1 may underlie some of this resistance, say Sunil Ahuja of the University of Texas Health Science Center, San Antonio, and his colleagues. They report in Science that individuals carrying extra copies of this gene are less likely to contract HIV or to progress to full-blown AIDS1.
The finding strengthens the prospect that, in future, people might be screened for this gene and others linked to HIV resistance. Those who are particularly vulnerable might, for example, be advised to follow a more aggressive course of therapy. "We are getting to a point where it would be worthwhile trying that," says geneticist Mary Carrington of the National Cancer Institute in Frederick, Maryland.
Patients could also be divided up according to their genetic make-up in trials for potential HIV vaccines, to identify groups most likely to respond. "It's a very nice piece of work, and very important," comments Michael Lederman, an infectious disease specialist at Case Western Reserve University in Cleveland, Ohio.
Scientists already know about a handful of other genes that are linked to HIV resistance, including one called CCR5. Normally, the virus latches on to CCR5 protein on the surface of some types of white blood cell, and uses it to get into the cell. Certain mutations in CCR5 render people far more immune to HIV.
CCL3L1, the gene identified in the new study, makes a protein that also binds to CCR5. Ahuja suggests that people with extra copies of this gene are more resistant to HIV because they make more CCL3L1, and cuts the amount of CCR5 around for the virus to attach to and therefore prevents it from entering white blood cells.
In the study, the team counted the number of gene copies in a range of populations from around the world. African populations have an average of six copies, whereas non-African populations have half that number, the researchers found.
They compared groups of HIV positive and negative people within different populations, and counted their gene copies. They found that, regardless of the absolute number of gene copies in a population, those with a below-average number within their population are more likely than their fellows to contract HIV, and more likely to develop AIDS if they are infected.
This heightened disease susceptibility is exacerbated in those who also have a 'high-risk' variation of the CCR5 gene. The team estimates that around 40% of the risk of HIV infection can be explained by these two genes.
And yet HIV researchers believe there is a range of other, as yet unidentified, genes that determine a person's susceptibility to HIV. "We're missing a whole bunch," says Ahuja.
A variety of non-genetic factors are also important. For example, infection by other sexually transmitted diseases is thought to boost the risk of picking up HIV.
- Gonzalez E., et al. Sciencexpress, 0.1126/science.1101160 (2004).