HIV’s surprising structure

The building blocks of the immature human immunodeficiency virus are arranged in a surprising way say researchers who have pinpointed the location of each block within the virus structure.

Cryo-electron microscopy images taken 20 years ago at the European Molecular Biology Laboratory (EMBL) revealed the HIV virus lacked the expected regular symmetrical structure, meaning obtaining a detailed picture of the protein lattice surrounding its genetic material would be difficult.

But by optimising how data is collected at the microscope and then analysed, researchers at the same institution have achieved an unprecedentedly detailed structure which they hope to use to concentrate efforts for exploring potential drug targets.

“The structure is definitely different from what we’d expected,” said John Briggs, who led the work. “We assumed that retroviruses like HIV and Mason-Pfizer Monkey Virus would have similar structures, because they use such similar building blocks, but it turns out their immature forms are surprisingly different from each other. At this point, we really don’t know why.”

Take a tour of an unprecedentedly detailed structure of the immature form of HIV http://youtu.be/eARxfwmoOC0

The structure, published in Nature, will now allow scientists to probe further, deciding where to focus efforts for achieving greater detail needed to explore possible drug targets, and to help them understand how mutations might influence how the virus assembles.

“This approach offers so many possibilities,” said Florian Schur, a PhD student in Briggs’ lab. “You can look at other viruses, of course, but also complexes and proteins inside cells, with a whole new level of detail.”

The team will how concentrate on other viruses and the vesicles that transport materials inside cells. They also hope to push the technique further to visualise other parts of the viral protein currently beyond their reach that are suspected to play a role in HIV maturation.

“In the long term, we’d also like to investigate how drugs which are known to inhibit virus assembly and maturation actually work,” Briggs said.

[caption id="attachment_40540" align="alignleft" width="600"] The building blocks in immature HIV (centre) are arranged differently from those of immature Mason-Pfizer Monkey Virus (left). To form the mature virus, HIV’s building blocks take on yet another arrangement (right). Credit: EMBL/F.Schur[/caption]

Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution