The HIV-1 nucleocapsid chaperone protein forms locally compacted globules on long double-stranded DNA
Journal article, 2021

The nucleocapsid (NC) protein plays key roles in Human Immunodeficiency Virus 1 (HIV-1) replication, notably by condensing and protecting the viral RNA genome and by chaperoning its reverse transcription into double-stranded DNA (dsDNA). Recent findings suggest that integration of viral dsDNA into the host genome, and hence productive infection, is linked to a small subpopulation of viral complexes where reverse transcription was completed within the intact capsid. Therefore, the synthesized dsDNA has to be tightly compacted, most likely by NC, to prevent breaking of the capsid in these complexes. To investigate NC's ability to compact viral dsDNA, we here characterize the compaction of single dsDNA molecules under unsaturated NC binding conditions using nanofluidic channels. Compaction is shown to result from accumulation of NC at one or few compaction sites, which leads to small dsDNA condensates. NC preferentially initiates compaction at flexible regions along the dsDNA, such as AT-rich regions and DNA ends. Upon further NC binding, these condensates develop into a globular state containing the whole dsDNA molecule. These findings support NC's role in viral dsDNA compaction within the mature HIV-1 capsid and suggest a possible scenario for the gradual dsDNA decondensation upon capsid uncoating and NC loss.


Kai Jiang

Chalmers, Biology and Biological Engineering, Chemical Biology

Nicolas Humbert

University of Strasbourg

Sriram Kesarimangalam

Chalmers, Biology and Biological Engineering, Chemical Biology

I. Rouzina

Ohio State University

Yves Mely

University of Strasbourg

Fredrik Westerlund

Chalmers, Biology and Biological Engineering, Chemical Biology

Nucleic Acids Research

0305-1048 (ISSN) 1362-4962 (eISSN)

Vol. 49 8 4550-4563

Subject Categories

Biochemistry and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Microbiology in the medical area





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6/3/2021 1