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Large-scale genetic analysis suggests that the answer lies in tiny changes in the structure of a protein that helps the immune system recognize and destroy infected cells.
HIV controllers — people with naturally strong immune systems
Most people infected with HIV eventually develop AIDS. The virus multiplies in its cells, eventually reaching a high level, and causes irreversible damage to the immune system. However, the virus does not progress in about one in three hundredths of infected people. These so-called HIV controllers have a natural immune system that suppresses viral replication.
The first person to think about the clinical significance of such controllers was Bruce Walker, an immunologist at Massachusetts General Hospital. “I realized that it is necessary to find out what people who develop the virus and those who pass it have in common,” he comments.
Walker and his colleagues examined the DNA of more than 900 HIV controllers. They compared samples with the genetic codes of 2,600 people with normal HIV infections. Scientists tracked changes in one “letter” of DNA at millions of points in the human genome and found more than three hundred sites that were statistically related to the fight against infection.
All specific objects were in the region of the genome that encodes proteins involved in the immune response, or rather HLA proteins. The researchers used regression analysis to narrow their search to the four sites most closely associated with HIV immunity.
It is impossible to say with certainty that only these areas are responsible for immunity. But by using a detailed map of HLA sites, scientists were able to identify specific amino acids in one of the proteins, called HLA-B, that differ between controllers and people with normal development infection. These amino acids have been shown to be able to control the virus.
HLA-B protein is the most important link
HLA-B plays an important role in the body's immune response to a viral attack. When viruses infect the body, they hijack cells to produce protein. HLA-B collects peptides, short fragments of these viral proteins, and carries them to the cell membrane, where they act as markers for immune system disruptor cells. Five of the six amino acids that differ between controllers and non-controllers are found in the structural lining used by HLA-B to bind viral proteins.
Smaller studies conducted in South Africa have already revealed the involvement of HLA-B in HIV immunity and these results now only confirm that HLA-B is the most important protein in Rodney Phillips, an immunologist at the Institute for Emerging Infections at Oxford University, comments on this process.
It remains unclear exactly how this process differs between controllers and non-controllers. “There is still plenty of work to do,” says Walker, “as we have yet to determine the exact mechanism by which this HLA-B fragment is active.” We are still a long way from creating a vaccine or prescribing a specific treatment. But we are optimistic about the future, as we now know what we need to control,” concludes the immunologist.