Tuesday, August 14, 2007

About 50% of Europeans carry one copy of a genetic mutation which appears able to reduce the amount of HIV in the body by an average of 60%

Roxanne Khamsi:

A small genetic mutation in the section of human DNA that codes for immune proteins appears able to reduce the amount of HIV in the body by an average of 90%, new research suggests. Scientists say the finding points to new ways in which vaccines might one day help boost immune protection against the virus.

Jacques Fellay at Duke University in Durham, North Carolina, US, and his teammates reviewed data collected from 30,000 HIV-infected individuals of European descent over a three-year period.

Within this group, the team identified almost 500 individuals who had a known date of infection and a stable amount of HIV in their system – a measure known as 'viral load'.

Working with the molecular biologist David Goldstein, Fellay sought to understand how genetic differences among these 500 people could influence how well their bodies kept HIV under control.

Using DNA sequences determined from patient blood samples, the team worked to link specific genetic mutations with differences in viral load. Their analysis revealed that one particular variant, in a part of the code that produces an immune protein called HLA-C, seems have a big impact on virus levels in the body.

People with this tiny sequence variation, dubbed rs9264942, appear to have up to 90% less virus in their systems than those who carry other polymorphisms.

Fellay says viral load is known to be the most important predictor for how quickly a person's infection will develop into full-blown AIDS. A patient whose virus levels initially settle at a lower number has a much better prognosis than someone whose infection stabilises at a higher amount, he explains.

The rs9264942mutation appears to help fight HIV infection by increasing the amount of HLA-C protein produced in the body. The protein helps alert the immune system to foreign particles, such as viruses, within cells. While HIV can disable similar proteins, known as HLA-A and HLA-B, it appears unable to do the same to HLA-C.

About 10% of Europeans appear to carry two copies of rs9264942, which leads to an average 90% viral load reduction. About 50% of Europeans carry one copy, which gives a 60% reduction. By comparison, less than 40% of people of African descent appear to carry a single copy of the polymorphism.

Fellay says that the new results from the study suggest that a vaccine to stimulate the action of HLA-C could help fight HIV.

Previous studies have found that certain genetic mutations, such the rare CCR5 mutation, can offer protection against the virus, but the new report is the first to show the impact of a variant affecting HLA-C.

The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele

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