WASHINGTON, Nov 5, (Agencies): 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.
“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, co-senior author of a study released Thursday.
“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,” added the director of the Ragon Institute of Massachusetts General Hospital.
For nearly 20 years, doctors have known that a small minority of HIV-infected individuals — about one in 300 — are naturally able to suppress viral replication with their immune system, keeping viral load at extremely low levels.
Genome
“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,” said Walker.
“Understanding where this difference occurs allows us to sharpen the focus of our efforts to ultimately harness the immune system to defend against HIV,” he added in the study published in Friday’s issue of Science magazine. Researchers led by Ragon Institute’s Florencia Pereyra enrolled 3,500 individuals in clinics around the world, including 2,500 with progressive HIV infection and 1,000 controllers — HIV infected people resistant to AIDS. Through a genome-wide association study, which tests variations at a million points in the human genome, the researchers identified some 300 sites that were statistically associated with immune control of HIV.
The sites were all in regions of chromosome 6 that code for so-called HLA proteins.
Without fully sequencing that genome region, which was unfeasible given the number of participants, the researchers developed a process that pinpointed specific amino acids that have a key role in viral control.
Further testing linked differences in five amino acids in the HLA-B protein to viral control mechanisms.
“Our work demonstrates that these variants could make a crucial difference in the individual’s ability to control HIV by changing how HLA-B presents peptides from this virus to the immune system,” said Walker.
Slight differences in five amino acids in a protein called HLA-B may explain why certain people resist the human immunodeficiency virus, US researchers said on Thursday in a study that lends new clues about how to make a vaccine to prevent AIDS.
“For a long time, we’ve known that some people progress extremely rapidly when they get infected, and others can stay well for three decades and never need treatment and still look entirely well,” said Dr. Bruce Walker of Massachusetts General Hospital and Harvard University, whose study appears in the journal Science.
Techniques
“We thought we could apply new techniques from the human genome project to understand what the genetic basis was for that,” he said. About one in 300 people infected with HIV can suppress the virus with the immune system, keeping the virus at extremely low levels.
The team 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.
That helped them identify some 300 different sites in the genetic code that were linked with immune control of HIV, all located on chromosome 6.
They narrowed that down to four single-letter changes in the DNA, known as single nucleotide polymorphisms or SNPs — pronounced “snips” — all related to the immune system.
“We did a second study where we looked amino acid by amino acid in that region,” Walker said.
They found five amino acids in the HLA-B protein linked with differences in a person’s ability to control HIV.
That protein is important for helping the immune system tag and destroy cells infected by a virus, and Walker said those genetic variants could make a big difference in a person’s ability to control HIV.
Knowing how some people mount an effective immune response to HIV could be an important step in understanding how to make a vaccine to fight the virus.
Cautions
It was not a vaccine yet, Walker cautions, but it is promising.
“We’ve got a clearer indication of why people can survive in the face of HIV, and we’ve gotten more focused in terms of the research we need to do to get where we’ve got to go,” he said.
No vaccine exists against the human immunodeficiency virus that causes AIDS. Since the AIDS pandemic started in the early 1980s, almost 60 million people have been infected with HIV, many of them in Africa, and it has killed 25 million.
In September 2009, scientists reported their biggest success yet with an experimental vaccine that showed a modest effect and appeared to slow the rate of infection by about 30 percent. In July, US researchers found antibodies that can protect against a wide range of AIDS viruses and said they may be able to use them to design a vaccine.