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  3. HIV-1 uncoating requires long double-stranded reverse transcription products

HIV-1 uncoating requires long double-stranded reverse transcription products

  • Sci Adv. 2024 Apr 26;10(17):eadn7033. doi: 10.1126/sciadv.adn7033.
Ryan C Burdick 1,  Michael Morse 2,  Ioulia Rouzina 3,  Mark C Williams 2,  Wei-Shau Hu 4,  Vinay K Pathak 1
Affiliations

Affiliations

  • 1 Viral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, 21702, USA.
  • 2 Department of Physics, Northeastern University, Boston, MA 02115, USA.
  • 3 Department of Chemistry and Biochemistry, Center for Retroviral Research and Center for RNA Biology, Ohio State University, Columbus, OH 43210, USA.
  • 4 Viral Recombination Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, 21702, USA.
PMID: 38657061 DOI: 10.1126/sciadv.adn7033
Abstract

HIV-1 cores, which contain the viral genome and replication machinery, must disassemble (uncoat) during viral replication. However, the viral and host factors that trigger uncoating remain unidentified. Recent studies show that infectious cores enter the nucleus and uncoat near the site of integration. Here, we show that efficient uncoating of nuclear cores requires synthesis of a double-stranded DNA (dsDNA) genome >3.5 kb and that the efficiency of uncoating correlates with genome size. Core disruption by capsid inhibitors releases viral DNA, some of which integrates. However, most of the viral DNA is degraded, indicating that the intact core safeguards viral DNA. Atomic force microscopy and core content estimation reveal that synthesis of full-length genomic dsDNA induces substantial internal strain on the core to promote uncoating. We conclude that HIV-1 cores protect viral DNA from degradation by host factors and that synthesis of long double-stranded reverse transcription products is required to trigger efficient HIV-1 uncoating.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-111964
    98.44%, HIV-1衣壳抑制剂
    HIV
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