Cyclophilin a prevents HIV-1 restriction in lymphocytes by blocking human TRIM5α binding to the viral core

Disruption of cyclophilin A (CypA)-capsid interactions affects HIV-1 replication in human lymphocytes. To understand the mechanism, we used Jurkat cells, human PBMCs, and human CD4+ T cells. Our results showed that the inhibition of HIV-1 infection caused by disrupting CypA-capsid interactions is dependent on human TRIM5α (TRIM5αhu), suggesting that TRIM5αhu restricts HIV-1. Accordingly, we found that TRIM5αhu binds to the HIV-1 core. Disruption of CypA-capsid interactions failed to affect HIV-1-A92E infection, correlating with the loss of TRIM5αhu binding to HIV-1-A92E cores. Disruption of CypA-capsid interactions in PBMCs and CD4+ T cells had a greater inhibitory effect on HIV-1 when compared to Jurkat cells. HIV-1-A92E infection of PBMCs and CD4+ T cells was unaffected by disruption of CypA-capsid interactions. Consistent with TRIM5α restriction, disruption of CypA-capsid interactions in CD4+ T cells inhibited reverse transcription. Overall, our results showed that CypA binding to the core protects HIV-1 from TRIM5αhu restriction.