Advanced Imaging Gives New Insight into HIV Infection
November 27, 2023
Key points:
- Researchers employed advanced imaging to characterize an elusive HIV protein structure and improve understanding of how the virus infects cells.
- Imaging of the binding between HIV envelope proteins and CD4 receptors showed that the envelope protein must bind to more than two CD4 receptors in order to infect the cell.
- This type of structural biology research is key for studying not only HIV, but also other different viruses.
The human immunodeficiency virus (HIV) is difficult to treat because it mutates rapidly and shields itself from recognition and attack by antibodies and therapeutics. However, if researchers can understand how HIV infects cells, they can design better treatment options.
Now, research published in Nature, uses advanced imaging to characterize an elusive HIV protein structure and improve understanding of how the virus infects cells.
When an HIV virion prepares to attack a T cell, its surface envelope protein undergoes shape-shifting changes. This envelope protein resembles a tripod-like flower with three “stem” portions called gp41 and three “petal” regions called gp120. The gp120 proteins initiate infection by grabbing onto T cell CD4 receptors and exposing sites that allow the virus to enter the cell.
In this study, researchers aimed to determine if altering CD4 binding could prevent HIV infection.
Using an innovative approach, the team devised a protocol to create stable heterotrimers. They then utilized cryo-electron microscopy to image the heterotrimers’ structures bound to CD4 receptors. Imaging of the binding between heterotrimers and CD4 receptors showed that the envelope protein must bind to more than two CD4 receptors in order to fully open, undergo the shape-shifting process, and infect the cell.
By collaborating with a lab at Yale University, they found that the behavior of the engineered heterotrimers in a test tube was remarkably similar to how envelope proteins on the viral surface behave in a “real world” infection scenario.
This type of structural biology research is important for studying HIV and many other kinds of viruses.
“The structures of these previously unknown, intermediate envelope conformations offer fascinating insights into structural changes driven by receptor interactions,” said Pamela Björkman, professor at Caltech. “Our research not only opens new avenues for exploring the complexities of HIV infection, but also provides valuable insights that extend beyond therapeutic design.”
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Source: https://www.laboratoryequipment.com/609001-Advanced-Imaging-Gives-New-Insight-into-HIV-Infection/
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