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.
Show 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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