HIV-1 infection induces Vif-mediated SUMOylation of host RNA splicing factors important for proper viral RNA splicing

• 成果类型: Article
• 署名作者: Kelenis, Demetra P.; Johnson, Jeffrey R.; Sidoli, Simone; Emery, Ann; Swanstrom, Ronald; Hawkins, Luke J.; Mckie, Kaila; Pawar, Tegh; Goff, Stephen P.
• 署名单位: Columbia University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Yeshiva University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; Columbia University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2532659123
• 发表日期: 2026-05-05
• 页码: e2532659123
• 关键词: SUMO; hiv-1; hnrnp; Vif; splicing; HNRNP A/B PROTEINS; messenger-rna; in-vivo; replication; conjugation; binding; A1; hypermutation; INTEGRASE; context

摘要

SUMOylation is a dynamically regulated post-translational modification involving covalent attachment of small ubiquitin-like modifiers (SUMOs) to lysine residues of target proteins. SUMOylation modulates multiple fundamental host cellular pathways, including pathways hijacked by HIV-1 to enable replication, but has not been explored by large-scale proteomics in the context of HIV-1 infection. Here, we performed a proteome-wide, mass spectrometry-based screen to identify proteins that are SUMOylated in response to HIV-1 infection. We show that infection with HIV-1 leads to the widespread increased SUMOylation of the heterogeneous nuclear ribonucleoprotein (HNRNP) A/B family. This phenotype was driven by expression of HIV-1 Viral Infectivity Factor (Vif), suggesting an unexplored function for this protein. Depletion of HNRNP A/B proteins led to altered splicing of HIV-1 viral RNAs and dramatically reduced HIV-1 infectivity. Our data suggest a mechanism involving HIV-1-induced, Vif-mediated SUMOylation of host RNA splicing factors as a means to regulate HIV-1 alternative splicing.