Gene Hope from HIV Controllers
posted: 05/11/2010
Scientists are closer to understanding why a tiny proportion of people with HIV can live for many years without treatment and without developing AIDS. New scientific insights could boost HIV vaccine and treatment prospects by exploiting natural immunity to the virus. But a UK HIV expert said there is still a "long way" to go before a vaccine or any new drug for HIV can be developed.
Natural immunity
About one in 300 people with HIV do not develop AIDS because of natural immunity. Their immune systems keep the virus in check, preventing HIV from overwhelming the body's immune system defences, and reducing the risk of passing on HIV.
People who stay healthy are described as "HIV controllers". Their bodies are able to control HIV by suppressing it so far that the viral load can be undetectable.
Genes of 1000 compared with 2,600
The latest study involved an exhaustive genome-wide genetic scan involving a million measurements of the DNA of 1000 HIV controllers from around the world. These were compared with the genomes of 2,600 other people with HIV. The comparison revealed significant differences in the DNA responsible for one of the immune system's vital proteins, called HLA-B. This is already known for defending the body against viruses.
Small differences
The study found that the ‘Controllers’ version of this protein has differences in only five of the amino acids – the building blocks of proteins. These differences are at the "binding pocket," which locks on to invading viruses, before warning the immune system that it is under attack.
HLA-B is part of the process by which the immune system recognises and destroys virus-infected cells. Part of the protein called a binding pocket "drags and drops" peptides from inside the virus onto the cell membrane. These then mark out the cell for destruction by CD8 "killer" T cells of the immune system.
"We found that, of the three billion nucleotides in the human genome, just a handful make the difference between those who can stay healthy in spite of HIV infection and those who, without treatment, will develop AIDS," said Bruce Walker, director of the Ragon Institute at the Massachusetts General Hospital in Boston.
Paul de Bakker of the Broad Institute in Cambridge, Massachusetts, said: "Earlier studies showed that certain genes involved with the HLA system were important for HIV control. But they couldn't tell us exactly which genes were involved and how they produced this difference. Our findings take us not only to specific protein, but to a part of that protein essential to its function."
One step closer
Dr Walker emphasised that the discovery just one of the major differences that increase people’s chance of living healthily with HIV.
"We've not identified the precise mechanism to explain HIV controllers, but we know that of all the genetic influences involved, this is by far the most important," Dr Walker said.
Doug tells us why he's involved
Doug Robinson, 46, from Truro, Massachusetts, is one of hundreds enrolled in the study of "HIV controllers". He was diagnosed in November 2003 but is still healthy and well. Normally by this stage of HIV infection, and without anti-HIV drugs, Mr Robinson would be expected to have a high level of HIV in his bloodstream – a "viral load" of about 50,000 copies of HIV. Instead, Mr Robinson has under 50 copies, which is undetectable.
"After my diagnosis, a friend told me that I am here for a purpose, that I could be a link to something that could be beneficial, and I felt like I had a responsibility to put myself out there," Mr Robinson said. "I feel it's my responsibility, no matter what I do, to put that to use. When I'm long gone, and the dust has blown over me, I hope to leave something, a positive contribution."
Hope but a long road
Gus Cairns, editor of HIV Treatment Update of the UK's National Aids Manual, said: "This research opens the door to the development of a vaccine that could encourage the body to mimic the most effective kind of immune response, or to drugs that could interfere with HIV's ability to infect cells and derange the immune system.
"Nonetheless there is still a lot we don't know about why some genetic variants provide a much less welcoming environment for HIV than others and, although we are becoming clearer about what kinds of specific immune response are effective against HIV, we are a long way from being able to make them happen, or even knowing what we must do to make them happen."
Sources and reference
Independent
BBC
HIV Controllers study
Science article (pay to view)
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