Researchers at Scripps Research and Los Alamos National Laboratory have developed a method to map sugar molecules on HIV. These sugars function as a shield from the immune system and mapping them will enable researchers to gain deeper insights on why antibodies respond differently to the virus, depending on location. The hope is these understandings will help with the future development of new vaccines that target vulnerabilities on HIV and other viruses. The sugar shields form on the outermost spike proteins of HIV and many other viruses, including SARS-CoV-2. These viruses have evolved sites on their spike proteins where glycan molecules readily attach.
"We now have a way to capture the full structures of these constantly fluctuating glycan shields, which to a great extent determine where antibodies can and can't bind to a virus such as HIV," says lead author Zachary Berndsen, PhD, a postdoctoral research associate at Scripps.
The scientists combined an atomic-scale imaging method called cryo-electron microscopy (cryo-EM) with computer modeling and a molecule-identifying technique called site-specific mass spectrometry. Cryo-EM utilizes the averaging thousands of individual snapshots to create a clear image, thus molecules like glycans will appear blurry, if at all. By adding cryo-EM with the other technologies, the researchers were able to recover this lost glycan signal and use it to map sites of vulnerability on the surface of Env.
"This is the first time that cryo-EM has been used along with computational modeling to describe the viral shield structure in atomic detail," says Srirupa Chakraborty, PhD, co-lead author and post-doctoral researcher in the Gnanakaran lab at Los Alamos National Laboratory.
Image Credit
Zachary Berndsen, PhD, Ward lab at Scripps Research