Genetic study shows how HIV controllers get their groove

By Ed Yong | November 4, 2010 2:00 pm


The vast majority of people who are infected with HIV go on to develop AIDS. Their bodies become riddled with the virus, their immune systems falter, and they are besieged by life-threatening infections. But not everyone shares the same fate. Around 1 in every 300 people infected with HIV carry genetic trump cards that allow them to resist and control the virus. These “HIV controllers” can live with the virus for years. They never develop AIDS and they live long, healthy lives, even if they never take any medication. Their genetic secrets are slowly being revealed.

Since 2006, a massive group of international scientists have been recruiting and studying a large group of HIV controllers from around the world as part of the International HIV Controllers Study. All of the recruits have been HIV-positive for 10 years. Despite that, the levels of the virus in their blood are around 50 times lower than expected and they have healthy levels of helper T cells, the immune cells that are normally hit by HIV.

Led by Florencia Pereyra, Xiaoming Jia and Paul McLaren, the team compared the genes of almost 1,000 controllers with those of over 2,600 people who haven’t been so lucky at subjugating the virus. After looking at over 1.3 million points around their genomes, the team found that just 313 separate the controllers from the other recruits.

Amazingly, every single one of these variants sits within a specific part of our sixth chromosome, among a set of genes called class I HLA genes. The proteins they produce form part of the internal security checks that defend us from infections. They grab small pieces of other proteins from inside our cells and display them on the outside, waving them under the noses of passing T-cells. If the T-cells recognise these pieces as parts of bacteria, viruses or other foreign invaders, they tell the infected cell to self-destruct and set the immune system on red alert.

All of this depends on a single groove in the HLA proteins. This is the bit that embraces the pieces of other proteins and displays them so prominently to the immune system. If this groove isn’t structured correctly, our defenders don’t get an advanced warning about threats.

True enough, the team found that the groove of a single protein called HLA-B is especially important. At five positions in the groove, the HIV controllers have different amino acids than those whose disease progresses normally. These five amino acids aren’t the only things separating the controllers from the others, but they have a major impact. One of them – the one at position 97 – is “associated with the most extremes of viral load” depending on the… amino acid [there].”

The link between these amino acids and the control of HIV is also very consistent. Pereyra did her protein comparisons using only the Europeans in her study (who formed the largest proportion of the sample). However, the results held true when she focused on the African-American group, and when she repeated the comparison in an independent group of HIV-infected Swiss patients. Again, people with different amino acids at certain key spots in HLA-B  proteins were more likely to keep the virus at bay.

It’s still not clear how exactly these genetic variations alter the shape of the HLA proteins, and how these changes affect the ability to control HIV. Nonetheless, the international study is off to a promising start and perhaps, it will help to inspire future vaccines or treatments against this most frustrating of foes.

Reference: Science
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Comments (9)

  1. Old Geezer

    Going from the specific to the general, is it possible that this could lead to gene therapy that would prevent all viruses from gaining a foothold? Is this another doorway to a cure for the common cold?

  2. Interestingly, AIDS “denialists”/”dissidents” often claim that science can’t explain the phenomenon of long term non progressors (people who don’t get ill despite testing HIV positive). Though I’m not holding my breath that this new study will change any minds over on that side…

    Just a wee bit of pedantry on an otherwise great post: When you say “The vast majority of people who are infected with HIV go on to develop AIDS” it would be good to qualify this with “if left untreated”.

  3. Brian Too

    Interesting! HIV resistant people are then much more common than I thought.

    My impression was that this attribute was a “one in a million” long shot.

  4. Shade

    These people don’t believe because they don’t want to.
    Givin enough time, all questions can be answered if you want the answer.

    So “These five amino acids aren’t the only things separating the controllers from the others, but they have a major impact. One of them – the one at position 97 – is “associated with the most extremes of viral load” depending on the… amino acid [there].””

    What exactly does this mean? I’m not sure I understand completely; if its the “wrong” amino acid then the virus goes undetected, but if its the “right” one, the virus should be purged yes? So why do these people test positive, yet remain basically healthy?
    Are the amino acid’s reprogramming the virus to be basically inert?

  5. pascal obiagwu

    their are some cuple that go for HIV test,the wife tested positive while the hosband tested negative dos it mean that the hosband has an immune system that can kill this virus or what?

  6. amphiox


    Maybe, but also remember that the likelihood of transmission is not 100% (I think it is actually less than 1% per exposure, and depends on the type of exposure as well).

    Also, do you know for certain from your sources that the couple in question aren’t using protection, or just abstaining?

  7. Thom

    @5 and 6:

    Don’t neglect the fact that the husband may be cheating and received the infection from a totally unknown, third party.

  8. Praedor

    #5: Some people have the good fortune of having mutant HIV receptor proteins, totally aside from the HLA proteins of this post (CCR5 and the like). These people can be repeatedly exposed to HIV and not get infected simply because the virus cannot use its prefered entry handles.

  9. PJ

    In fact, the wife MUST have received the infection from a third party. That’s pretty much how it works. :-)

    Also, remember that HIV tests won’t come up positive until a few months after the initial infection. It’s possible that the husband is already infected, even though he tests negative.

    I was under the impression that the vast majority of people infected with HIV *were* left untreated. I took that sentence as a subtle reminder of the fact.


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