In situ chromatin dynamics and HIV-1 nuclear trafficking.

Area of Science:

• Cell Biology
• Structural Biology
• Virology

Background:

• Nuclear architecture and chromatin organization influence macromolecular transport.
• Human immunodeficiency virus type 1 (HIV-1) nuclear import requires navigating complex nuclear environments.

Purpose of the Study:

• To visualize chromatin structure and HIV-1 core behavior during nuclear import in situ.
• To elucidate the relationship between chromatin dynamics and HIV-1 nuclear trafficking.

Main Methods:

• Correlative cryo-electron tomography combined with a functional nuclear import system.
• High-resolution imaging of native nucleosomes and viral cores within intact nuclei.

Main Results:

• Identified four structural classes of nucleosomes, revealing a heterogeneous and dynamic chromatin landscape.
• HIV-1 cores exclude nucleosomes and preferentially associate with open chromatin structures.
• Disruption of CPSF6-capsid interactions prevents association with open chromatin, trapping cores peripherally.

Conclusions:

• Established an in situ framework linking chromatin structure and dynamics to HIV-1 nuclear transport.
• Provided a structural basis for how HIV-1 navigates the dynamic nuclear landscape.
• Highlighted the role of specific viral-host interactions in directing viral trafficking.