Extra copies of gene protect against HIV

US scientists have identified a genetic variation that partly explains people's different susceptibility to HIV (human immunodeficiency virus), the virus that causes AIDS (Acquired Immune Deficiency Syndrome). The findings could help doctors tailor treatment to their patients' genetic make-up, say the team, who published their results in the early online edition of the journal Science. Scientists have known for several years that some people are naturally resistant to HIV, and the latest research identifies one of several different genes thought to be involved.

When infected with HIV, some people develop full-blown AIDS within months, whereas others can remain symptom-free for years. There are also differences in people's initial susceptibility to the virus. Scientists have been trying to pinpoint the genes involved in HIV resistance, to help develop vaccines and more effective treatments. A team based at the University of Texas Health Science Center has now shown that people who have extra copies of a gene called CCL3L1 are less likely to contract HIV, or to develop AIDS once they are infected with the virus.

The researchers counted the number of CCL3L1 gene copies in over 4,300 HIV-positive and negative African, European and Hispanic people. They found that African populations have an average of six copies of the gene, while non-African populations have an average of three. But the absolute number of gene copies did not matter - within each population, people who had fewer than the average number of copies were more likely to contract HIV, and more likely to develop AIDS if infected.

The CCL3L1 gene makes a protein that sticks on to another protein called CCR5, which sits on the surface of some types of white blood cell, and acts as an 'entry-point' for HIV. Team leader Sunil Ahuja thinks that people who make extra CCL3L1 protein have less CCR5 protein available for the virus to attach to. This means that there are fewer entry points for the virus, so it cannot get into white blood cells so readily, making these people more resistant to HIV.

The researchers also found that the people most susceptible to HIV had a 'high-risk' version of the CCR5 gene, in addition to fewer copies of the CCL3L1 gene. They think that between them, these two genes account for around 40 per cent of the risk of HIV infection. Other genes, yet to be identified, are thought to be involved, as well as non-genetic factors such infection by other sexually transmitted diseases. 'If we understand the differences in genetic variations, we might be able to generate vaccines with stronger effects', said team member Matthew J Dolan. He also said that better knowledge of a person's genetic defences 'could be used to make decisions about tailoring therapy for individual persons'.