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

作者：Manuel García-Moreno, Azman Embarc-Buh, Robin Truman, Marko Noerenberg, Louisa Iselin, Honglin Chen, Caroline E. Lenz, Jeffrey Y. Lee, Kate Dicker, Snehith Dyavari Shetty, Natasha Palmalux, Quan Gu, Thibault J. M. Sohier, Aino I. Järvelin, Wael Kamel, Vincenzo Ruscica, Emiliano P. Ricci, Ilan Davis, Shabaz Mohammed, Alfredo Castelló · 发表于：Cell Reports · 年份：2026 · DOI：10.1016/j.celrep.2026.117090 · 被引用次数：12 · 研究领域：RNA Research and Splicing、HIV Research and Treatment、RNA modifications and cancer

The initial steps of the human immunodeficiency virus type 1 (HIV-1) life cycle are regulated by cellular RNA-binding proteins, but only a few have been identified. Here, we developed in virion RNA interactome capture (ivRIC) to comprehensively profile the direct protein interactors of the HIV-1 genomic (g)RNA inside the viral particles. We identified 104 cellular RNA-binding proteins in virions (ivRBPs), many of which are nuclear. We determined the interactome of the viral RBP Rev and discovered that nuclear ivRBPs may associate gRNA in the nucleus and continue bound after the genesis of the viral particles. We also observed that ivRBPs are not incorporated into viral particles based on their abundance, but likely through selective mechanisms. Moreover, we show that the ivRBPs PURA and its homolog PURB control HIV-1 particle infectivity and engage with several viral proteins and key elements within HIV-1 gRNA, showcasing the importance of ivRBPs for HIV-1 infection.