Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

• Published in: Nature communications 2016-05, Vol.7 (1), p.11568-11568, Article 11568
• Main Authors: Grime, John M. A., Dama, James F., Ganser-Pornillos, Barbie K., Woodward, Cora L., Jensen, Grant J., Yeager, Mark, Voth, Gregory A.
• Format: Article
• Language: English
• Subjects: 119/118; 631/114; 631/326/596/2148; 631/57/2272/2276; Capsid - metabolism; Capsid protein; Capsid Proteins - genetics; Capsid Proteins - metabolism; Cytoplasm; Dismantling; Equilibrium; HIV; HIV-1 - physiology; Human immunodeficiency virus; Humanities and Social Sciences; Infectivity; Intermediates; Maturation; Molecular Dynamics Simulation; Morphology; multidisciplinary; Nucleation; Physiology; Protein Multimerization - physiology; Proteins; Ribonucleic acid; RNA; RNA, Viral - metabolism; Science; Science (multidisciplinary); Self-assembly; Simulation; Viral infections; Virus Assembly - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11568

The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies. Significant morphological changes occur during the conversion of the immature HIV virion into a mature infectious form. Here the authors use coarse-grained molecular dynamics simulations to model HIV-1 capsid self-assembly and disassembly events that suggests several metastable capsid intermediates sensitive to local conditions.