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Friday, December 4, 1998 Published at 00:13 GMT


Sci/Tech

The genetic acceleration of Aids



Scientists have discovered why some people infected with HIV develop the symptoms of Aids more quickly than others.

The discovery is already being used to develop new drugs that could give Aids sufferers several more years of healthy life.

A team from the US National Cancer Institute has shown that a change in a small stretch of DNA known as a promoter appears to accelerate the progression to Aids more quickly in certain people.

A promoter sits in front of a gene and allows it to be 'read out' by an enzyme to produce a protein.

In this instance, the particular promoter helps to express the CCR5 gene which makes chemokine receptor molecules that sit on the surface of cells.

The molecules are supposed to pick up chemical signals sent to cells, but they also the give the Aids virus a means of attack.

Rapid progression

"We've shown that a [change in a] promoter region next to the CCR5 gene seems to be associated with more rapid progression to Aids," said Dr Mary Carrington, from the institute.

"CCR5 is a chemokine receptor, that is a receptor for chemical signals and its normal function is to bind chemokines, chemical signals which induce the movement of white cells to the site of an injury. But CCR5 has also been shown to be a receptor for HIV, through which HIV infects cells."

The change in the promoter makes it drive the CCR5 gene to work harder to produce more receptors.

Thus, if people who have inherited the altered form of the CCR5 promoter become infected with HIV, then the virus will spread more rapidly from white blood cell to white blood cell inside them.

Their immune systems, which consist mainly of white blood cells, will be destroyed more rapidly and they will develop the symptoms of Aids several years earlier than other people.

Promoter type

The scientists studied five groups of patients with Aids, which included Caucasians and African Americans, and found that those carrying the changed promoter known as CCR5P1 progressed to Aids more rapidly than those with other types of the CCR5 promoter.

They say between 7% and 13% of all people fall into the most susceptible category.

Whilst the research has helped to explain the development of the disease in some people, it has also opened an avenue to attack HIV.

If a drug were made which could deny HIV access to the CCR5 receptors, those infected with the virus might have extra years of healthy life before they succumbed to the symptoms of full-blown Aids.

"A number of drug companies are already trying to look at ways to administer chemokines or derivatives to block the binding of HIV to the CCR5 receptors," said Dr Carrington.

"After chemokines bind to receptors they down-regulate, switch off the gene that makes the receptors. So another possibility is to make drugs that mimic that effect. So there are possibilities."

The research is published in the journal Science.





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