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

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03106108
Contributor : Francesca Di Nunzio <>
Submitted on : Monday, January 11, 2021 - 3:42:24 PM
Last modification on : Saturday, January 16, 2021 - 6:00:02 PM
Long-term archiving on: : Monday, April 12, 2021 - 7:06:12 PM

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Anastasia Selyutina, Mirjana Persaud, Lacy Simons, Angel Bulnes-Ramos, Cindy Buffone, et al.. Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5α Binding to the Viral Core. Cell Reports, Elsevier Inc, 2020, 30 (11), pp.3766-3777.e6. ⟨10.1016/j.celrep.2020.02.100⟩. ⟨pasteur-03106108⟩

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