Genes shed light on body's response to HIV

An international team of researchers has identified immune system genes that seem to play a key role in the body's defence against human immunodeficiency virus (HIV), the virusthat causes acquired immunodeficiency syndrome (AIDS). The scientists, who published their results in the journal Nature, say their findings should help efforts to develop an effective vaccine for the disease. The study also partly explains how some people can contract the HIV virus, but remain free of symptoms for years.

HIV attacks the body's immune system, disarming the its defences against infections and certain cancers. The virus attacks and kills crucial immune system cells, known as T-helper cells. Without T-helper cells, many other immune system cells cannot not work properly, including B-cells that make antibodies. So people with AIDS have difficulty fighting off infections that would cause relatively minor problems in healthy individuals.

In the latest study, the researchers looked at genes that make human leucocyte antigen (HLA) molecules, which sit on the surface of body cells. When a cell is infected with a virus, the HLA molecules bind to fragments of viral proteins, and 'display' them on the outside of the cell. This brings the infected cell to the attention of the body's 'killer' T cells, which will then destroy it. The scientists wanted to see if variations in the genes that make HLA molecules could account for differences in how well the immune system deals with HIV.

The team looked at blood samples from 375 HIV-infected patients at the Doris Duke Medical Research Institute at the University of KwaZulu-Natal, in South Africa. They found that different versions of an HLA gene called HLA-B corresponded to significant differences in the way the body coped with HIV infection, whereas differences in the HLA-A and HLA-C genes had no effect. They also looked at more than 700 chronically infected African HIV patients, and found that particular versions of the HLA-B gene were associated with high or low levels of the virus in the blood.

The researchers also found that HIV positive women who have a protective version of HLA-B are more likely to survive, and less likely to pass the virus on to their children. 'HLA-B is where all the action is', said team leader Philip Goulder. He said that most vaccines take no account of the differences between HLA-A and HLA-B genes, adding 'These may be critical to the success or failure of a vaccine'.

Goulder also said that the results could explain why HLA-B molecules have been changing more rapidly than other HLA molecules - in response to infectious diseases, including HIV. 'We are witnessing the evolutionary fight between the human immune system and the HIV virus happening right now', he added. Jo Robinson, of the Terence Higgins Trust, a UK HIV charity, welcomed the study. However, she stressed that 'we are many years away from having a vaccine for HIV'.