How HIV stays one step ahead of immune system

Researchers seeking a vaccine find that the virus that causes AIDS quickly evolves into different strains to battle different populations' genetic makeups.
$ G8 f( t7 T' R9 sBy Mary Engel
February 28, 2009
. N/ B, m# n6 x4 X# JHIV, the virus that causes AIDS, is one of the fastest-evolving entities known. That's why no one has yet been able to come up with a vaccine: The virus mutates so rapidly that what works today in one person may not work tomorrow or in others.
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3 u1 l/ H) L( UA study published Wednesday in the journal Nature confirms that dizzying pace of evolution on a global scale.

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Booster Shots: The Times' health blog"It's very clear there's a battle going on between humans and this virus, and the virus is evolving to become unrecognized by the immune system," said Dr. Bruce Walker, one of the researchers and director of the Ragon Institute, at Massachusetts General Hospital in Boston. "It does make clear what a huge challenge making a vaccine is."

HIV evolves to escape the immune system, much in the same way that bacteria mutate under pressure by antibiotics, Walker said.

. p' R8 e5 _) T* E% }" AResearchers looked at HIV genetic sequences in the United Kingdom, South Africa, Botswana, Australia, Canada and Japan to see how they evolved in response to a key set of molecules in the human immune system, called human leukocyte antigens. These molecules direct the immune system to recognize and kill HIV and other infectious diseases.

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Genes that encode human leukocyte antigens vary among humans, and even small differences can dramatically affect a person's response to HIV infection. For example, an adult infected with HIV will survive on average about 10 years without anti-HIV drugs before developing acquired immune deficiency syndrome. But some people will progress to AIDS within a year, and others can survive without treatment for 20 years.

The study published online Wednesday found that mutations occurred not just in individuals but on a population level. That is, if a particular genetic immune sequence was common in a population, the HIV mutation that evolved to escape it became the most common strain of HIV, even in those without that particular human leukocyte antigen gene.
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"What this study does is give an explanation for why there are different HIV strains in different parts of the world," Walker said. "The genetic makeup of people in different regions is influencing the virus in specific ways."
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! y7 s3 W. Y# o% W3 M4 n; E7 p) YThis would appear to be bad news for the director of the newly opened Ragon Institute of MGH, MIT and Harvard, which was founded to develop vaccines for HIV and other infectious diseases.
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% F) s0 w: g5 }- y  x: tBut Walker saw the results as hopeful. He said that mutations can actually make the virus less fit -- that is, unable to replicate as quickly or do as much damage. His challenge is to find what kind of pressure results in this kind of mutation.

Researchers from the Ragon Institute, Oxford University in England, Kumamoto University in Japan, and Royal Perth Hospital and Murdoch University in Australia analyzed the genetic sequences of HIV and human leukocyte antigen genes in 2,800 people total.

http://www.latimes.com/news/nati ... sci-hiv28-2009feb28,0,7364282.story