In a breakthrough, scientists have mapped the most detailed images yet of the protein responsible for getting HIV into cells, paving way for a potential vaccine for AIDS.
The new findings of the AIDS-causing virus’s complex envelope, includes sites that future vaccines will try to mimic to elicit a protective immune response.
Scientists at The Scripps Research Institute (TSRI) and Weill Cornell Medical College determined the first atomic-level structure of the tripartite HIV envelope protein long considered one of the most difficult targets in structural biology and of great value for medical science.
“Most of the prior structural studies of this envelope complex focused on individual subunits; but we’ve needed the structure of the full complex to properly define the sites of vulnerability that could be targeted, for example with a vaccine,” said Ian A Wilson, a senior author of the study.
HIV, the human immunodeficiency virus, currently infects about 34 million people globally, 10 per cent of whom are children, according to World Health Organisation estimates.
Although antiviral drugs are now used to manage many HIV infections, especially in developed countries, scientists have long sought a vaccine that can prevent new infections and perhaps ultimately eradicate the virus from the human population.
However, none of the HIV vaccines tested so far has come close to providing adequate protection. This failure is due largely to the challenges posed by HIV’s envelope protein, known to virologists as Env.
Env’s structure is so complex and delicate that scientists have had great difficulty obtaining the protein in a form that is suitable for the atomic-resolution imaging necessary to understand it.
“It tends to fall apart, for example, even when its on the surface of the virus, so to study it we have to engineer it to be more stable,” said biologist Andrew Ward.
The research team was able to engineer a version of the Env trimer (three-component structure) that has the stability and other properties needed for atomic-resolution imaging, yet retains virtually all the structures found on native Env.
Using cutting-edge imaging methods, electron microscopy and X-ray crystallography, the team was able to look at the new Env trimer.
The X-ray crystallography study was the first ever of an Env trimer, and both methods resolved the trimer structure to a finer level of detail than has been reported before.
The data illuminated the complex process by which the Env trimer assembles and later undergoes radical shape changes during infection and clarified how it compares to envelope proteins on other dangerous viruses, such as flu and Ebola.