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Genome survey provides clue to HIV's 'Achilles heel'

By Steve Connor, Science Editor Published: 20 July 2007

Three genetic alterations in people infected with HIV may have given them some protection against Aids, scientists say.

The discovery, made during a survey of the human genome, could lead to a better understanding of how an effective vaccine for the virus can be developed which helps to prevent HIV from attacking and overwhelming the body's immune defences.

Some people infected with HIV take longer than others to develop full-blown Aids and the scan of the human genome suggests that variations in the DNA of the genes may play a key role in helping some people to remain healthy for longer than others.

Scientists found the three DNA variants by analysing the entire genomes of 486 people who, although infected with the virus, seemed to have been able to fend off or delay the onset of full-blown Aids.

It is the first time that a scan of the entire human genome has been performed to study resistance to an infectious disease and it could mark a new milestone in the fight against Aids and the development of an effective vaccine, say the scientists, who are part of a large international collaboration.

"These results not only approximately double our understanding of the factors that influence variation amongst individuals in how they control HIV-1, but also point toward new mechanisms of control," said David Goldstein of Duke University Medical Centre in Durham, North Carolina. "As we expand the number of patients in future studies ... we aim to discover even more polymorphisms [variations] that could provide additional clues how some patients are better able to control the virus than others. This should ultimately lead to novel targets for vaccines."

Polymorphisms are natural variations in the DNA of genes that determine differences in genetic traits between people. It is possible to find these individual polymorphisms as a result of knowing the complete map of the human genome.

Two of the polymorphisms found in the study, published yesterday in the journal Science, were in genes controlling a part of the immune system called the human leukocyte antigen (HLA) system, which plays a major role in identifying foreign "invaders" in the blood and tagging them for destruction. Two of the HLA genes - HLA-A and B - are switched off by HIV when it enters the body, which keeps the immune system from recognising the virus as foreign, Professor Goldstein said.

A third gene, HLA-C, however, is not thought to be turned off by HIV. As a result, HLA-C may turn out to be the Achilles heel of HIV, which could be used to manufacture a working vaccine, he said.

"This study was the first time a genome-wide approach has been used for an infectious disease. Past studies have looked at individual candidate genes," Professor Goldstein said.

"Since different people respond differently to infections, a better understanding of how immune system genes control responses to infections should help us to design better treatments and more effective vaccines," he said.

Blood samples taken during the period immediately after infection were analysed. Variations in the amount of virus in the blood during this period before patients were given anti-viral drugs showed how well their own immune systems coped with the initial infection.

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