The Env protein, which the virus uses when it binds to cells, is included in these detailed findings, which include 3D views of the structure and position of the virus’ envelope “spike” proteins in the context of the full virus. Proteins that have been isolated from viruses or expressed in the lab are commonly referred to as “engineered proteins” by scientists. They also shed new light on glycan shields—the sugars on proteins that can hide it from the body’s immune system—as another important development.
According to lead author Kelly Lee, associate professor of medicinal chemistry in the University of Washington School of Pharmacy, “We’re looking at the whole virus particle and how this protein on the surface relates to the rest of the virus,” Lee explained. It’s also possible to see how the virus’s “face” is displayed and how it would be recognized or hidden from the immune system if we look at the virus’s complete structure.
The scientists were able to learn more about the Gag lattice, the virus’s internal protein structure, because they could see the virus in its entirety.
According to Lee, “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,” At the very least, we now have the correct architectural model for how a virus is put together. This interaction still needs to be worked out in more detail.”
As a result of this discovery, the paper’s title — “Cryo-ET of Env on intact HIV virions reveals structural variations and positioning on the Gag lattice” — appeared in the journal Cell on February 4th. The “stalk” supporting the envelope proteins is flexible and can tilt, presenting both opportunities and challenges to the immune system’s neutralizing antibodies that protect cells from infection, according to another finding that had not previously been observed.
According to co-author Michael Zwick, an associate professor of immunology and microbiology at Scripps Research Institute, “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,”
Because the virus has so few spikes and disguises them with sugar molecules, it is an extremely difficult target for vaccine development, according to Zwick.
According to Lee, a researcher at the University of Washington, “All these features increase the dynamic variability that the HIV spike protein presents to the immune system,” Since the beginning of HIV vaccine development, this has been a problem for those who work on it: the virus is constantly mutating and evolving. There are literally thousands of different variants in each person infected, and this multiplies even further across populations.”
A more lethal strain of HIV was discovered in the Netherlands earlier this year. Fortunately, despite being a “highly virulent variant,” the strain responds to treatment.
Just another reminder of how quickly these viruses evolve, so we need scientists to keep studying them, Zwick said.
