With the help of a supercomputer and a clever algorithm, scientists can now pinpoint how specific viral mutations allow HIV to hide from the body’s defences, and thereby wreak havoc within cells.

The researchers believe that their new study provides a “cheat-sheet” detailing the stealthy moves the virus can make, and that their results could therefore help other researchers develop an effective AIDS vaccine.

Because the human immune system cannot easily monitor what is occurring inside our cells, it relies on proteins called human leukocyte antigens, or HLAs to help keep track of this activity. HLAs help with this detective work by picking up protein fragments within cells and bringing them to the cell surface, where the immune system can decide if something is going wrong inside the cell.

So, for example, an HLA protein might pick up fragments of HIV and present these bits at the surface, prompting the immune system to destroy the cell. The big problem is that HIV can mutate rapidly within the body, enabling it to escape detection by certain HLA variants.


To make matters even more complicated, 500 different variations of HLA exist in the human population – individuals inherit one form of the molecule from each parent. So knowing how well an individual’s immune system will detect and destroy a certain mutated form of HIV becomes a tricky task.

Linking vulnerabilities

Zabrina Brumme of the Partners AIDS Research Center in Boston, Massachusetts, US and her collaborators decided to use maths to shed some light on this complex problem. They began their study by taking blood samples from about 700 HIV-infected individuals in Canada.

In general, the volunteers in the trial had been infected for at least five years, but had only just shown signs of a weakened immune system.

For this reason, when they donated their blood samples for the experiment, none of them had yet started taking antiretroviral drugs. So any mutations researchers found in the virus represented HIV trying to evade the immune system, rather than it developing resistance to medication.

Brumme and her colleagues analysed the virus fragments in the blood samples and determined the genetic sequence of the HIV within each person. They also identified each individual’s HLA type.

Next, they turned to 250 linked-up computers to run a complex statistical analysis to understand how people with certain HLA types are more vulnerable to specific variants of HIV.

Brumme says it would have taken a standard desktop computer at least a year to run the same calculation. Importantly, the sophisticated statistics allowed researchers to control for other factors besides HLA type that would influence the prevalence of certain HIV strains.

Defeating HIV diversity

The number-crunching linked up specific changes in the HIV sequence with certain HLA types. For example, people with HLA type B57 are prone to developing HIV strains that code for the amino acid glutamic acid inside of valine at position 245 in the viral sequence.

Brume says that the information from the study will help scientists in their quest to create a vaccine against HIV infection. “One of the major challenges that HIV researchers face is the massive diversity of this virus,” she says.

Knowing which versions of the virus will trigger the immune system, and which ones will successfully evade it, is important when designing a vaccine, Brumme explains. Vaccines succeed only when they stimulate an immune response.

Journal reference: PLoS Pathogens (DOI:10.1371/journal.ppat.0030094)

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