Scientists identify genes that enable some immune systems to halt HIV; finding could spur drug, vaccine development

Nov 8 2010

"Tiny variants in a protein that alerts the body to infection could explain how one in 300 HIV-infected people are able to resist the onset of AIDS for years without needing any treatment, researchers said Thursday" in a study published online in the journal Science, Agence France-Presse reports (11/4). "The findings are encouraging for the development of vaccines because they tell scientists how the immune system might be manipulated to fend off HIV," the Independent writes (Connor, 11/5).

"HIV is slowly revealing its secrets ... Knowing how an effective immune response against HIV is generated is an important step toward replicating that response with a vaccine," said Bruce Walker of Massachusetts General Hospital, who was a senior co-author on the study, AFP adds. "We have a long way to go before translating this into a treatment for infected patients and a vaccine to prevent infection, but we are an important step closer," he said (11/4).

For nearly two decades scientists have recognized "that a small minority ... of individuals infected with HIV are naturally able to suppress viral replication with their immune system, keeping viral load at extremely low levels," according to a Massachusetts General Hospital press release (11/4).  Such individuals, referred to by researchers as "'HIV controllers' do not require treatment, because their bodies suppress the replication of the virus," Nature News writes (Milton, 11/4). Science News adds, "Scientists have long thought that finding the genetic peculiarities underlying this protection could help to create drugs or a vaccine against HIV" (Seppa, 11/4).

In search of the genetic differences that enable some immune systems to suppress the HIV virus, an international consortium of researchers "searched the genetic makeup of nearly 1,000 people with that ability and compared it with the genetic code of 2,600 others who were infected with HIV" and not HIV controllers, Reuters reports (Steenhuysen, 11/4). "The controllers had variations in five amino acids in a protein called HLA-B, which alerts the immune system to the presence of infection," HealthDay/Bloomberg BusinessWeek reports.

"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," Walker explained, the Massachusetts General Hospital press release adds. "Understanding where this difference occurs allows us to sharpen the focus of our efforts to ultimately harness the immune system to defend against HIV."

Though "[e]arlier studies had showed that certain genes involved with the HLA system were important for HIV control … they couldn't tell us exactly which genes were involved and how they produced this difference. Our findings take us not only to a specific protein, but to a part of that protein that is essential to its function," Paul de Bakker of Brigham and Women's Hospital, also a senior co-author on the study, said, according to the press release (11/4).

"This is a really exciting step toward a kind of pie-in-the-sky goal," statistical geneticist Alison Motsinger-Reif of North Carolina State University, who was not involved in the study, said, according to Science News. "Elite controllers represent a medical mystery, she sa[id]. 'If we can understand what's different about their biology, it will open up new targets [for HIV] drugs or vaccines,'" she said, the news service writes (11/4).

However, Walker "emphasized discovery is not like a 'light switch' that turns someone into an HIV controller. It is one factor among several that increases the chances of someone being able to survive for many years with HIV and not antiretroviral treatment, he said," the Independent writes.  "We've identified a major determinant but there are other factors that will influence the pathway. 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," Walker said, according to the newspaper (11/5).

The Philadelphia Inquirer, also reporting on the findings of the HIV controller study, tells the story of the contributions made by patients who are HIV controllers to become testing subjects in order to advance scientists' understanding of how to best fight the HIV virus (Flam, 11/5).