Human cytosolic extracts stabilize the HIV-1 core

Thomas Fricke, Alberto Brandariz-Nuñez, Xiaozhao Wang, Amos B. Smith, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The stability of the HIV-1 core in the cytoplasm is crucial for productive HIV-1 infection. Mutations that stabilize or destabilize the core showed defects on HIV-1 reverse transcription and infection. We developed a novel and simple assay to measure the stability of in vitro-assembled HIV-1 CA-NC complexes. The assay allowed us to demonstrate that cytosolic extracts strongly stabilize the HIV-1 core. Interestingly, stabilization of in vitro-assembled HIV-1 CA-NC complexes is not due solely to macromolecular crowding, suggesting the presence of specific cellular factors that stabilize the HIV-1 core. By using our novel assay, we measured the abilities of different drugs, such as PF74, CAP-1, IXN-053, cyclosporine, Bi2 (also known as BI-2), and the peptide CAI, to modulate the stability of in vitro-assembled HIV-1 CA-NC complexes. Interestingly, we found that PF74 and Bi2 strongly stabilized HIV-1 CA-NC complexes. On the other hand, the peptide CAI destabilized HIV-1 CA-NC complexes. We also found that purified cyclophilin A destabilizes in vitro-assembled HIV-1 CA-NC complexes in the presence of cellular extracts in a cyclosporine-sensitive manner. In agreement with previous observations using the fate-of-the-capsid assay, we also demonstrated the ability of recombinant CPSF6 to stabilize HIV-1 CA-NC complexes. Overall, our findings suggested that cellular extracts specifically stabilize the HIV-1 core. We believe that our assay can be a powerful tool to assess HIV-1 core stability in vitro.

Original languageEnglish (US)
Pages (from-to)10587-10597
Number of pages11
JournalJournal of virology
Volume87
Issue number19
DOIs
Publication statusPublished - 2013

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Fricke, T., Brandariz-Nuñez, A., Wang, X., Smith, A. B., & Diaz-Griffero, F. (2013). Human cytosolic extracts stabilize the HIV-1 core. Journal of virology, 87(19), 10587-10597. https://doi.org/10.1128/JVI.01705-13