Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5α Binding to the Viral Core

Anastasia Selyutina, Mirjana Persaud, Lacy M. Simons, Angel Bulnes-Ramos, Cindy Buffone, Alicia Martinez-Lopez, Viviana Scoca, Francesca Di Nunzio, Joseph Hiatt, Alexander Marson, Nevan J. Krogan, Judd F. Hultquist, Felipe Diaz-Griffero*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Disruption of cyclophilin A (CypA)-capsid interactions affects HIV-1 replication in human lymphocytes. To understand this mechanism, we utilize human Jurkat cells, peripheral blood mononuclear cells (PBMCs), and CD4+ T cells. Our results show that inhibition of HIV-1 infection caused by disrupting CypA-capsid interactions is dependent on human tripartite motif 5α (TRIM5αhu), showing that TRIM5αhu restricts HIV-1 in CD4+ T cells. Accordingly, depletion of TRIM5αhu in CD4+ T cells rescues HIV-1 that fail to interact with CypA, such as HIV-1-P90A. We found that TRIM5αhu binds to the HIV-1 core. Disruption of CypA-capsid interactions fail to affect HIV-1-A92E/G94D infection, correlating with the loss of TRIM5αhu binding to HIV-1-A92E/G94D cores. Disruption of CypA-capsid interactions in primary cells has a greater inhibitory effect on HIV-1 when compared to Jurkat cells. Consistent with TRIM5α restriction, disruption of CypA-capsid interactions in CD4+ T cells inhibits reverse transcription. Overall, our results reveal that CypA binding to the core protects HIV-1 from TRIM5αhu restriction.

Original languageEnglish (US)
Pages (from-to)3766-3777.e6
JournalCell reports
Volume30
Issue number11
DOIs
StatePublished - Mar 17 2020

Keywords

  • capsid
  • CD4 T cells
  • core
  • cyclosporine A
  • CypA
  • HIV-1
  • restriction
  • reverse transcription
  • TRIM5α
  • uncoating

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Selyutina, A., Persaud, M., Simons, L. M., Bulnes-Ramos, A., Buffone, C., Martinez-Lopez, A., Scoca, V., Di Nunzio, F., Hiatt, J., Marson, A., Krogan, N. J., Hultquist, J. F., & Diaz-Griffero, F. (2020). Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5α Binding to the Viral Core. Cell reports, 30(11), 3766-3777.e6. https://doi.org/10.1016/j.celrep.2020.02.100