Interactome of the HIV-1 proteome and human host RNA

The human immunodeficiency virus (HIV-1) is highly dependent on a variety of host factors. Beside proteins, host RNA molecules are reported to aid HIV-1 replication and latency maintenance. Here, we implement multiple workflows of native RNA immunoprecipitation and sequencing (nRIPseq) to determine direct host RNA interaction partners of all 18 HIV-1 (poly)proteins. We identify 1,727 HIV-1 protein - human RNA interactions in the Jurkat cell line and 1,558 interactions in SupT1 cells for a subset of proteins, and discover distinct cellular pathways that seem to be used or controlled by HIV-1 on the RNA level: Tat binds mRNAs of proteins involved in the super elongation complex (AFF1-4, Cyclin-T1). Correlation of the interaction scores (based on binding abundancy) allows identifying the highest confidence interactions, for which we perform a small-scale knockdown screen that leads to the identification of three HIV-1 protein binding RNA interactors involved in HIV-1 replication (AFF2, H4C9 and RPLP0). Several host RNA molecules have been reported to aid HIV-1 replication and latency maintenance. Here, native RNA immunoprecipitation and sequencing was applied to comprehensively identify direct host RNA interaction partners for all 18 HIV-1 (poly)proteins.The in-depth interactome of the full HIV-1 proteome and host RNA identifies over 3000 interactions across two T-cell lines.HIV-1 Tat interactors are enriched for members of the super elongation complex.A small-scale KD screen identified three HIV-1 protein RNA interactors involved in HIV-1 replication (AFF2, H4C9 and RPLP0). Several host RNA molecules have been reported to aid HIV-1 replication and latency maintenance. Here, native RNA immunoprecipitation and sequencing was applied to comprehensively identify direct host RNA interaction partners for all 18 HIV-1 (poly)proteins.