Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice.

ABSTRACT: Lenacapavir (GS-6207; LEN) is a potent HIV-1 capsid inhibitor approved for treating multidrug-resistant infection. LEN binds to a hydrophobic pocket between neighboring capsid (CA) proteins in hexamers and stabilizes the capsid lattice, but its effect on HIV-1 capsids is not fully understood. Here, we labeled HIV-1 capsids with green fluorescent protein fused to CA (GFP-CA) or a fluid-phase GFP content marker (cmGFP) to assess LEN's impact on HIV-1 capsids. HIV-1 cores labeled with GFP-CA, but not cmGFP, could be immunostained with an anti-GFP antibody and were less sensitive to the capsid-binding host restriction factor MX2, demonstrating that GFP-CA is incorporated into the capsid lattice and is a marker for capsid lattice stability, whereas cmGFP is an indicator of core integrity. LEN t

SUBMITTER: Li C 

PROVIDER: S-EPMC12002175 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature