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Updated: Aug 22, 2025
Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging
Published on: December 1, 2011
Cryo-EM structures of prefusion SIV envelope trimer
Jason Gorman1, Chunyan Wang2,3, Rosemarie D Mason1
1Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution.
Insights
Simian immunodeficiency viruses (SIVs) use variable loops and glycan shields on their envelope (Env) trimers to evade immune responses. These structures reveal conserved mechanisms of immune evasion across SIV evolution.
Area of Science:
- Virology
- Structural Biology
- Immunology
Background:
- Simian immunodeficiency viruses (SIVs) are lentiviruses infecting non-human primates, serving as the origin for HIV-1 and HIV-2.
- Understanding SIV envelope (Env) structure is crucial for insights into lentiviral evolution and immune evasion.
Purpose of the Study:
- To determine the prefusion structure of SIV envelope trimers.
- To define the role of variable loops and glycans in SIV immune evasion.
- To investigate SIV Env structure in complex with neutralizing antibodies.
Main Methods:
- Prefusion stabilization of SIV envelope trimers.
- Cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET).
- Analysis of N- and O-linked glycan interactions and antibody binding.
Main Results:
- High-resolution cryo-EM structures of SIVmac Env trimers, including complexes with antibodies.
- Detailed mapping of SIV-specific disulfide-bonded variable loops (V1/V2) and their coverage.
- Identification of N- and O-linked glycans forming the Env-glycan shield, with O-linked glycans binding jacalin.
- Cryo-ET structures of SIVmac Env trimers on virions in ligand-free and antibody-bound states.
Conclusions:
- The prefusion-closed structure of the SIV Env trimer has been defined.
- Variable loops and glycan shields are key mechanisms for SIV immune evasion, conserved across the virus.
- These findings provide a structural basis for understanding SIV-host interactions and developing interventions.
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