Incorporation of genome-bound cellular proteins into HIV-1 particles regulates viral infection

Garcia-Moreno, M.; Truman, R.; Chen, H.; Iselin, L.; Lenz, C. E.; Lee, J.; Dicker, K.; Noerenberg, M.; Sohier, T. J. M.; Palmalux, N.; Jaervelin, A. I.; Kamel, W.; Ruscica, V.; Ricci, E. P.; Davis, I.; Mohammed, S.; Castello, A.

doi:10.1101/2023.06.14.544764

bioRxiv · 10.1101/2023.06.14.544764

Incorporation of genome-bound cellular proteins into HIV-1 particles regulates viral infection

Garcia-Moreno, M.·Truman, R.·Chen, H.·Iselin, L.·Lenz, C. E.·Lee, J.·Dicker, K.·Noerenberg, M.·Sohier, T. J. M.·Palmalux, N.·Jaervelin, A. I.·Kamel, W.·Ruscica, V.·Ricci, E. P.·Davis, I.·Mohammed, S.·Castello, A.

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Abstract

The initial steps of the human immunodeficiency virus 1 (HIV-1) lifecycle are regulated by cellular RNA-binding proteins (RBPs). To understand the scope of these early host-virus interactions, we developed in virion RNA interactome capture (ivRIC), which allowed the comprehensive and systematic profiling of the proteins that interact with the HIV-1 genomic (g)RNA inside viral particles. ivRIC identified 104 cellular RBPs within the encapsidated HIV-1 ribonucleoprotein, many of which are typically found in the cellular nucleus. Notably, these nuclear RBPs interact with the HIV-1 RBP Rev, suggesting that they associate with HIV-1 gRNA during its nuclear life. Functional assays show that ivRBPs are important for HIV-1, including PURA and PURB, which control viral gene expression and infectivity through interaction with critical sequences in the gRNA. Our characterisation of the composition of the encapsidated ribonucleoprotein of HIV-1 uncovers new host-virus interactions that invokes new mechanisms for controlling HIV-1 infection.

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Garcia-Moreno, M., Truman, R., Chen, H., Iselin, L., Lenz, C. E., Lee, J., Dicker, K., Noerenberg, M., Sohier, T. J. M., Palmalux, N., Jaervelin, A. I., Kamel, W., Ruscica, V., Ricci, E. P., Davis, I., Mohammed, S., Castello, A.. 2023-06-14. Incorporation of genome-bound cellular proteins into HIV-1 particles regulates viral infection. https://doi.org/10.1101/2023.06.14.544764

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