New Details About HIV Structure May Help with Vaccine Development

Investigators at the University of Washington and Scripps Research analyzed the basic architecture of HIV just above and below the surface. After examining 3D views of the structure and position of the virus’ spike proteins, the researchers classified the protein particles separate from the virus or expressed as engineered or purified proteins.

The team also discovered more information about glycan shields, which are the sugars on the proteins that enable it to avoid detection by the body’s immune system.

“We’re looking at the whole virus particle and how this protein on the surface relates to the rest of the virus,” said lead author Kelly Lee, associate professor of medicinal chemistry in the UW School of Pharmacy, in a press release. “And by looking at the intact virus structure, we can see how the different facets of this ‘face of the virus’ are being displayed and how they would be recognized by or hidden from the immune system.”

The new view of the virus also helped the researchers analyze the positioning of the envelope spike protein on the surface relative to the internal protein structure, called the Gag lattice.

“This finding overturns previous models of how the parts of the viruses are assembled and helps to focus our attention on where the docking interaction of these two proteins is likely to be,” Lee said in the press release. “This interaction needs to be resolved in more detail, but at least the current work gives us the correct architectural model for the virus assembly.”

Prior research was not able to identify the “stalk” supporting the envelope proteins and their flexibility, which presents potential flaws that can be exploited by the immune system’s neutralizing antibodies to protect cells from infection, according to the investigators.

“Structural biology has driven HIV vaccine design, so as we get a better and better picture of what it is we’re targeting, that inspires innovation and may lead to improved vaccines,” said co-corresponding author Michael Zwick, associate professor of immunology and microbiology at Scripps Research, in the press release.

Zwick added that HIV’s envelope is a challenge to target for vaccine development because the virus displays so few spikes and hides them with sugar molecules to avoid detection by the immune system.

“All these features increase the dynamic variability that the HIV spike protein presents to the immune system,” Lee said in the press release. “This is something that people in HIV vaccine development have grappled with from the very beginning — this virus mutates and changes itself astronomically and rapidly. Each time it infects an individual, you end up with literally thousands of different variants within that one individual, and if you look across populations, it’s multiplied even more.”

REFERENCE

Unexpected findings detailed in new portrait of HIV. University of Washington. February 16, 2022. Accessed February 22, 2022. https://www.washington.edu/news/2022/02/16/unexpected-findings-detailed-in-new-portrait-of-hiv/