For the first time, researchers have imaged the protein spikes that HIV uses to infect cells, which are notorious for continually changing conformation and resisting attacks by drugs. By monitoring these changes, scientists could find a new means of attacking the virus that could lead to new drugs or even vaccines. Two new papers have been published, describing the spikes. James Munro of the Yale University School of Medicine was lead author of the paper in Science, while Marie Pancera of NIAID was lead author of the paper in Nature.
The surface protein spikes help anchor the virus to cells, allowing its genetic material to safely enter a human cell, causing infection. The spikes consist of two molecules, gp120 and gp41, arranged in three pairs. Scientists have known about the structure of these molecules for years, but incredibly powerful microscopes have finally allowed them to image the proteins on the viral envelope for the first time.
These spikes make it incredibly difficult for the virus to be detected because they are constantly in motion, creating a moving target that is very hard to hit. To add another level of difficulty in combatting the virus, the spikes can open or close, and are only detectable when open. When the spikes are in a “closed” conformation, they are shielded from attacks by the immune system. The spikes do make the virus vulnerable and open for a brief time, just before attaching to a cell for infection. By only opening for a limited time, the virus is able to better protect itself from detection by antibodies.
“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,” Walther Mothes of Yale University, a senior author of both papers, said in a press release.
The fact that these spikes continually change shape has been incredibly problematic for drug or vaccine development. Having images of the spikes and tracking them over time will allow researchers to gain a better understanding of these movements, and could possibly provide an avenue for exploitation.
“The determination of the structure of this closed configuration of the HIV spike protein and the direct visualization of its fast openings represent a major step forward for drug and vaccine design,” Mothes said.
The researchers state that a small group AIDS have antibodies that force the virus to remain closed. While the virus doesn’t get eradicated by antibodies that way, it also prohibits the virus from causing an infection. If scientists could develop a way to target the spikes while they are closed, it could present a very exciting opportunity for prevention or treatment of HIV infection.
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