In situ chromatin dynamics and HIV-1 nuclear trafficking

The organization and dynamics of chromatin within intact nuclei remain poorly defined, limiting understanding of how nuclear architecture influences macromolecular transport. HIV-1 provides a striking example of a large complex that must traverse this dynamic landscape to access integration sites within transcriptionally active regions. Here, we combine a functional nuclear import system with correlative cryo-electron tomography to visualize chromatin architecture and HIV-1 cores in situ during nuclear penetration. Native nucleosomes resolved at 5.6 Å reveal four structural classes, from compact conformations at the nuclear periphery to open, flexible forms in the interior, defining a spatially heterogeneous and dynamic chromatin landscape. Within this environment, HIV-1 cores decorated with nuclear factors exclude nearby nucleosomes and preferentially associate with open chromatin. Disruption of CPSF6–capsid interactions abolishes these associations, confining viral cores to peripheral chromatin. These findings establish an in situ framework linking chromatin structure and dynamics to HIV-1 nuclear trafficking and provide a structural basis for viral navigation within the dynamic nuclear landscape.