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Friday, October 10, 2014

Constantly-changing protein that allows HIV to elude our immune system

For the first time, researchers have been able to monitor in high resolution the constantly-changing protein that allows HIV to elude our immune system, an important step towards creating a vaccine against the virus.
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This diagram shows the protein that HIV uses to infect cells in the "closed" and hidden state that it uses to elude our immune system.
Image: National Institute of Allergy and Infectious Diseases
HIV is so good at eluding our immune system and foiling any potential vaccines because the protein it uses to infect our cells is constantly changing.

Now scientists have managed to strip back the cloak and see this surface spike protein clearly for the first time ever.

The study, led by researchers from the US National Institute of Health, Weill Cornell Medical College and Yale University, has provided high resolution images of the movement and complete structure of these spikes, which HIV uses to bind with cells. The results were published simultaneously in Science and Nature this week.

"Now we can see how this fusion machine works, and in a general way it is similar to how fusion works in influenza and Ebola," said Walter Mothes from Yale University, the co-senior author of the Science paper, in a press release.

The research has revealed that each spike is made up of three sets of a pair of molecules, called gp120 and gp41. And, importantly, the scientists found that the configuration of the spikes changes before and after fusing with cells.

In order to fuse with and infect cells, this spike protein needs to be in an "open state", the researchers found. But when it's in its closed state, it's less visible to antibodies - so it only opens at the last possible moment to avoid being detected by the immune system.

The discovery suggests that any future HIV vaccine, one of the Holy Grails of medical research, would need to target the closed version the HIV spike proteins.

The press release explains:

Taken together, the scientists say, the findings indicate that an effective HIV vaccine that teaches the immune system to neutralise the virus should be based on the ground-state, pre-fusion form of the spike. Knowing the atomic structure of that configuration now gives researchers the tools to design and manipulate such a vaccine component. 

"The determination of the structure of this closed configuration of the HIV spike protein and the direct visualisation of its fast openings represent a major step forward for drug and vaccine design," said Mothes.

The research also explains why there's a rare class of antibodies, discovered in very few AIDS patients, which offers protection against the disease. These neutralising antibodies keep the spike protein in its closed state and prevent the spread of the virus, Mothes explains.
Sources: EurekAlert and EurekAlert (again)