HIV-1 Capsid Shape, Orientation, and Entropic Elasticity Regulate Translocationinto the Nuclear Pore Complex

Abstract

Nuclear import of the viral capsid is a critical step in the HIV-1 life cycle that serve to transport and release genomic material into the nucleus. Nuclear Pore Complex (NPC) allows passage of intact capsid, though mechanistic details of the process remain to be fully understood. Here we investigate the factors regulating HIV-1 capsid translocation into the NPC central channel using coarse-grained molecular dynamics simulations. We find that successful translocation is contingent on the compatibility of the capsid morphology and channel dimension and the proper orientation of the capsid approach to the channel. The central channel dynamically expands to allow capsid passage, demonstrating the pleomorphic nature of the channel necessary for transporting large cargoes. Structural analysis shows that stress induced by the central channel confinement and uncondensed internal genomic material generates correlated striated patterns of lattice disorder across the viral capsid surface which is an indicator of its lattice "elasticity". Our results suggest that the "elasticity" can aid the capsid to adapt to the stress and remain structurally intact during translocation. TeaserComputer Simulations identify capsid elasticity as a key factor for successful nuclear entry.