The human immunodeficiency virus (HIV) particle buds from the membrane of infected cells in an immature state and develops infectivity through a process termed maturation. This highly orchestrated restructuring of the virion's interior assembles a capsid packaging proteins and genetic material essential for propagating the virus. Although the structure of the virion in the immature and mature states is well determined, the molecular mechanisms that facilitate this transition have been difficult to probe experimentally. Here, we report the complete molecular pathway of HIV maturation. We reconstructed a model of the entire virion using atomically detailed structures. Coarse-grained (CG) topology and force field optimizations for computational efficiency enabled measurements of the long-timescale kinetics of critical mechanisms. Our simulations delineate the spatiotemporal dynamics of proteolytic cleavage and bridge the Gag lattice decomposition pathway to the self-assembly of the viral capsid. The model parameters can be used to emulate the effects of current maturation inhibitors, and leveraged to explore new therapeutic strategies.
Lee et al. (Sun,) studied this question.