HIV weakness revealed

Developing a vaccine against HIV has proven difficult because the virus is capable of rapidly mutating. However, researchers in America think they’ve found a weakness which undermines the virus’ fitness.

Ragon Institute researchers identified potential HIV vaccine targets in a subunit of the Gag protein. Six of those subunits come together to form the hexagonal proteins that make up the viral capsid Credit Vincent Dahirel

Researchers at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard University have identified regions of the HIV protein where mutations could affect the virus’ ability to survive and reproduce.

“Even though we have treatments, the number of people in need globally is outpacing our ability to provide these drugs,” said Bruce Walker, director of the Ragon Institute. “The only real solution is development of an effective vaccine.”

Using a mathematical approach – including random matrix theory – the Ragon team analysed available HIV proteins obtained from infected patients, focussing on the polyprotein Gag which gives the virus its structure.

Previous vaccine efforts have focussed on single mutations within amino acids; however, the team took a broader approach and tried to determine whether groups of amino acids within viral proteins evolve together in a coordinated way. Gag showed five co-evolving groups, and the researchers looked at each pair of sites within the groups, calculating whether a double mutation was beneficial or detrimental to the virus’ survival.

One group – in what researchers called sector-3 – had the highest proportion of detrimental multiple mutations. Amino acids in sector-3 are located at interfaces between proteins that form the viral capsid surrounding the virus’ genetic material.

“If you make multiple mutations to these amino acids, it’s difficult for the virus to assemble the capsid,” said Arup Chakraborty from MIT.

After testing their findings against human clinical data, researchers discovered T cells – which attack cells that display viral proteins on their surfaces – in patients who control HIV without medication target sector-3 amino acids at multiple points. HIV strains with multiple mutations in this sector are rare, indicating these strains are less likely to survive.

The researchers believe vaccines based on the vulnerabilities they discovered in Gag may be effective, and are looking for vulnerable targets in other HIV proteins. The work was published in Proceedings of the National Academy of Sciences.