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bioRxiv · 10.1101/678037

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

Selyutina, A.·Persaud, M.·Bulnes-Ramos, A.·Buffone, C.·Scoca, V.·Di Nunzio, F.·Hiatt, J.·Krogan, N. J.·Hultquist, J. F.·Diaz-Griffero, F.
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Abstract

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 TRIM5 (TRIM5hu), suggesting that TRIM5hu restricts HIV-1. Accordingly, we found that TRIM5hu binds to the HIV-1 core. Disruption of CypA-capsid interactions failed to affect HIV-1-A92E infection, correlating with the loss of TRIM5hu 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 TRIM5 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 TRIM5hu restriction.

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Selyutina, A., Persaud, M., Bulnes-Ramos, A., Buffone, C., Scoca, V., Di Nunzio, F., Hiatt, J., Krogan, N. J., Hultquist, J. F., Diaz-Griffero, F.. 2019-06-21. Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5α Binding to the viral Core. https://doi.org/10.1101/678037

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