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Updated: Aug 26, 2025

Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes
Published on: February 22, 2017
Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection
Guochao Wei1, Naseer Iqbal2, Valentine V Courouble3
1Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
None:
Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short phenylalanine-glycine (FG) containing peptides with isolated capsid hexamers have been characterized, how these cellular factors functionally engage with biologically relevant mature HIV-1 capsid lattices is unknown. Here we show that prion-like low complexity regions (LCRs) enable avid CPSF6, NUP153 and SEC24C binding to capsid lattices. Structural studies revealed that multivalent CPSF6 assembly is mediated by LCR-LCR interactions, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. In infected cells, avid CPSF6 LCR-mediated binding to HIV-1 cores is essential for functional virus-host interactions. The investigational drug lenacapavir accesses unoccupied hydrophobic pockets in the complex to potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results establish previously undescribed mechanisms of virus-host interactions and antiviral action.
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