Researchers Witness High-Speed HIV-1 Protein Movement
Antibodies aimed at this moving part could be key to a new vaccine approach.
Complete the form below to unlock access to ALL audio articles.
It’s not that we did anything wrong based on what we knew;
lead author, Rory Henderson
it's just that we didn't know it moves this way until now.
Once both molecules of the virus are bound to the cell membrane, the process of injecting viral RNA can begin. “Because HIV-1 is an integrating virus, blocking this process completely is essential to prevent infection,” Henderson said.
“If you get infected, you’ve already lost the game because it’s a retrovirus,” Bennett agrees.
The moving structure they found protects the sensitive co-receptor binding site on the virus. “It's also a latch to keep it from springing until it's ready to spring,” Henderson said. Keeping it latched with a specific antibody would stop the process of infection.
To see the viral parts in various states of open, closed and in-between, Bennett and Henderson used an electron accelerator at the Argonne National Laboratory outside Chicago that produces X-rays in wavelengths that can resolve something as small as a single atom. But this expensive, shared equipment is in high demand. The AIDS researchers were awarded three 120-hour blocks of time with the synchrotron to try to get as much data as they could in marathon sessions. “Basically, you just go until you can’t anymore,” Bennett said.
Earlier research elsewhere had argued that antibodies were being designed for the wrong shapes on the virus and this work shows that was probably correct.
“The question has been ‘why, when we immunize, are we getting antibodies to places that are supposed to be blocked?’” Henderson said. Part of the answer should lie in this particular structure and its shape-shifting.
“It’s the interplay between the antibody binding and what this shape is that's really critical about the work that we did,” Henderson said. “And that led us to design an immunogen the day we got back from the first experiment. We think we know how this works.”
Reference: Bennett AL, Edwards R, Kosheleva I, et al. Microsecond dynamics control the HIV-1 Envelope conformation. Sci Adv. 2024;10(5):eadj0396. doi: 10.1126/sciadv.adj0396
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
