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Updated: Feb 11, 2026

Structure of HIV-1 Capsid Assemblies by Cryo-electron Microscopy and Iterative Helical Real-space Reconstruction
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Structure of HIV-1 Capsid Assemblies by Cryo-electron Microscopy and Iterative Helical Real-space Reconstruction

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Multiple Pathways in Capsid Assembly.

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    Hepatitis B virus capsid assembly pathways were tracked in real time. Charge detection mass spectrometry revealed multiple assembly routes, with some intermediates stalling under specific conditions, indicating energy landscape minima.

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    Area of Science:

    • Virology
    • Biophysics
    • Structural Biology

    Background:

    • Virus capsid assembly is crucial for viral replication but poorly understood.
    • Icosahedral capsids, like Hepatitis B virus (HBV), assemble from numerous identical protein subunits.
    • Kinetic accessibility of assembly pathways is essential for spontaneous self-assembly.

    Purpose of the Study:

    • To investigate the real-time assembly pathways of the Hepatitis B virus (HBV) capsid.
    • To understand how protein subunit interactions influence capsid assembly dynamics.
    • To identify potential intermediate species and their role in the assembly process.

    Main Methods:

    • Utilized charge detection mass spectrometry (CDMS) for real-time monitoring of HBV capsid assembly.
    • Analyzed assembly under varying salt conditions to modulate subunit interaction strength.
    • Observed mass distributions of assembly intermediates and final products.

    Main Results:

    • Identified multiple assembly pathways for the HBV T=4 capsid.
    • Under moderate conditions, assembly proceeded without significant intermediate accumulation, suggesting downhill energy pathways.
    • High salt conditions induced a bifurcation, leading to stalled 90-dimer intermediates and near-complete capsids, indicating local energy minima.

    Conclusions:

    • HBV capsid assembly is not a single, linear process but involves multiple kinetically accessible pathways.
    • Stalled intermediates under specific conditions highlight the presence of local minima on the assembly energy landscape.
    • Understanding these pathways and intermediates offers insights into viral assembly mechanisms and potential therapeutic targets.