Cryo-EM structures of prefusion SIV envelope trimer

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.