HIV Changes to Hide From Immune Cells

New research published in Science (2002;296;5572:1439-1443) suggests that HIV eludes the body's defense system by changing in response to proteins called HLA molecules found on the surface of "killer" T-cells that target the virus. "Our study suggests that much of the enormous genetic diversity of HIV has been driven by the genetic diversity of HLA," said Dr. Simon A. Mallal, of the Royal Perth Hospital in Australia.

HLA markers, which vary from person to person, are involved in the body's ability to distinguish its own cells from those of foreign invaders. HIV is difficult to treat or prevent because it mutates so often, Mallal pointed out, noting that each of the 473 patients in the study had a different HIV DNA sequence. "The mutations were changing the amino acids, or building blocks, of the virus so as to prevent recognition by the particular HLA molecules present in the patient," Mallal explained.

For example, patients with one type of HLA typically had a mutation in a certain position of the reverse-transcriptase gene of HIV. "This is reminiscent of the way the virus mutates in characteristic spots of the gene to become resistant to the effects of antiviral drugs," Mallal said.

The research also sheds some light on why levels of HIV in the blood vary from person to person, he said. "It appeared that those viruses that had been more successful in mutating to avoid presentation by the HLA molecules of the patient could replicate themselves readily without being eliminated by the immune system," Mallal stated.

"The fact that HIV is an astounding escape artist has now been confirmed at a population level," wrote Drs. Andrew McMichael and Paul Klenerman of the University of Oxford in a related editorial. This is "worrying news" for controlling HIV infection and developing a vaccine, they stated. HIV's ability to mutate to evade HLA proteins shows that any vaccine will have to trigger wide-ranging responses "in order to stay one step ahead of HIV variation," they concluded.

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