AIDS Care Watch

Wednesday, May 07, 2008

Why some carriers don't get sick

By, Charlie Fidelman, Montreal Gazette, May 5, 2008

Despite the odds, a tiny group of people infected with the human immunodeficiency virus manage to stay healthy, never showing symptoms of illness.

So what is shielding this special group of HIV-infected people, dubbed "elite controllers," whose bodies control HIV so well the virus remains virtually undetectable? A team of Canadian and U.S. scientists believes it has solved part of the mystery.

Led by Rafick-Pierre Sékaly of the Centre Hospitalier de Université de Montréal, the team has discovered a "memory T cell" mechanism that protects these rare patients from viral diseases.

Published in the advance online edition of the journal Nature Medicine, the researchers explain how a protein in some people's DNA shields against life-threatening immune illnesses.

Moreover, when injected into sick tissue, this key protein - once modified - was able to reverse cell death in defective HIV cells.

The discovery means researchers might have a reliable target for an HIV vaccine, experts said.

It also opens the door to finding new therapies for other killer immune diseases.

"We're also focusing on cancer, another problem for which you need memory T cells," said Elias Haddad, adjunct professor in microbiology and immunology at U de M and McGill University.

Here's how it works: First, it's important to know that HIV infection is characterized by the slow death of memory T cells, which are vital in the defence against immune diseases, Haddad said.

The study compared three groups: an HIV-negative sample, an HIV-positive group whose infection was under control with medication, and a third group (the elite controllers) whose HIV showed no symptoms.

"They were better than healthy," Haddad said of the elites.

The secret of the elite controllers lies in a key protein called FOX03a. This protein induces "bad genes" to kill T cells, Haddad said. But in the elite group, which can fend off HIV infection without medication, the immune system remained resilient "keeping an anti-viral memory," Haddad explained.

That's because the FOX03a protein failed to get into the cell nucleus. Instead, the protein was targeted for destruction, he said.

It also worked in reverse to rescue cells.

"You can induce a long-term survival of memory cells in patients whose cells would otherwise die faster, and improve their quality of life," he said.

The immunological factor discovered by Sékaly's team could turn out to be helpful against other viral infections, said renowned AIDS researcher Mark Wainberg, head of the McGill AIDS Centre.

"It's an excellent study and an important discovery in terms of potential for long term solutions."

An estimated one out of 300 people infected with HIV are considered elite controllers, but they're largely invisible to AIDS researchers because they do not get sick.

Sékaly's team is recruiting elite controllers to take part in the next study. It can be reached at



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