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

Anastasia Selyutina (1) , Mirjana Persaud (1) , Lacy Simons (2) , Angel Bulnes-Ramos (1) , Cindy Buffone (1) , Alicia Martinez-Lopez (1) , Viviana Scoca (3) , Francesca Di Nunzio (3) , Joseph Hiatt (4, 5) , Alexander Marson (6, 7, 8) , Nevan Krogan (4, 5) , Judd Hultquist (2) , Felipe Diaz-Griffero (1)

1 Albert Einstein College of Medicine [New York]
2 Northwestern University Feinberg School of Medicine
3 Virologie moléculaire et Vaccinologie
4 QBI - Quantitative Biosciences Institute [UC San Francisco, USA]
5 David Gladstone Institutes [San Francisco]
6 UC San Francisco - University of California [San Francisco]
7 Innovative Genomics Institute
8 Chan Zuckerberg BioHub [San Francisco, CA]

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.

Domaines: Sciences du Vivant [q-bio]

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, 2020, 30 (11), pp.3766-3777.e6. ⟨10.1016/j.celrep.2020.02.100⟩. ⟨pasteur-03106108⟩