Genetic Variants Hold HIV in Check

When NOVA viewers met Bob Massie more than a decade ago in Surviving AIDS, he was a medical mystery: Infected with HIV in 1978, Massie hadn't developed any AIDS symptoms. Now, scientists have identified the genetic variations that help Massie and other like him keep HIV in check.

Controllers have a variant form of the HLA-B protein, pictured here, which helps flag infected cells. Credit: P. de Bakker

Massie is a member of an elite minority of HIV patients called controllers. Representing only one in 300 infected individuals, controllers have HIV, but their immune systems curb the virus' replication. Controllers don't get sick, and they are less likely to transmit HIV to others. For two decades, scientists have been trying to understand how controllers stave off AIDS. Their goal: New therapies that could help all patients defend against HIV.

Now, a genome-wide association analysis of nearly 1,000 controllers has homed in on minute variations in a protein called HLA-B. HLA-B is a "reconnaissance" protein; it flags virus-infected cells so that "killer" T cells can identify and destroy them. But controllers' HLA-B proteins are just a little bit different: Five amino acids that make up part of HLA-B's flagging mechanism frequently vary between controllers and the vast majority of HIV-infected individuals.

The new results, which represent the combined efforts of more than 300 scientists on six continents (just check the authors list--it's almost longer than the paper!) were published earlier this month in Science Express.

Massie and Bruce Walker, one of the leaders of the genome study, first met in 1994. Here's how they described that first meeting for NOVA:

BOB MASSIE: I didn't know what to expect. And he came in, and he was such a friendly and interested fellow, and when we started to describe what my situation was and he looked at some of the numbers that had come back or that I'd brought with me, he was so excited and so enthusiastic that it was actually quite charming.

BRUCE WALKER, MD: He came, said, I've been infected for 16 years, but I feel great, I've never taken any drugs. We thought that was already interesting. But when we got his viral load back, we became incredibly interested.

Controllers like Massie are lucky: When it comes to fighting HIV, they are genetically gifted. Though it's a long road from understanding the genetics of this immune response to testing a new HIV therapy, the more than 1,500 controllers who have already signed on with the International HIV Controllers Study are hoping that their good fortune will one day translate into better therapies for HIV. You can learn more about the results via the International HIV Controllers Study newsroom, which archives press releases as well as media coverage, and the many affiliated institutions, including the Broad Institute and the Ragon Institute.

User Comments:

Had the thought the other day that HIV might be a navigational beacon for switching off the human immune system one day. The ability to fight and fight and fight every conceavable genetic material is how we envision the strengthening of immunity, but perhaps we'll find an external immune system that works better and instead, we will seek ways to turn off our internal immunity... in which case we may look to HIV for its secrets.

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