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通过TGF-β诱导,HIV-1 Vpr通过TGF-β诱导来调节ciTRAN的上调

Aditi Choudhary¹, Katyayani Mallick¹, Rishikesh Dalavi¹

¹Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal, India.

|July 9, 2025

概括

艾滋病毒-1 Vpr 蛋白诱导TGF-β,通过SMAD信号通路调节前病毒性circRNA ciTRAN. 准TGFBR1降低了ciTRAN和病毒基因表达,影响了HIV-1复制.

科学领域:

病毒学病毒学
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

循环RNA (circRNA) 表达在HIV-1感染细胞中很普遍,但其与细胞信号通路的相互作用尚不清楚.
特定circRNAs在HIV-1病原发生中的作用需要进一步阐明.

研究的目的:

研究HIV-1感染,circRNA表达和细胞信号通路之间的联系.
确定HIV-1感染期间调节circRNA产生的机制.

主要方法:

对HIV-1感染细胞中circRNA表达的分析.
研究HIV-1 Vpr蛋白在TGF-β产生和circRNA上调调节中的作用.
在SMAD2/3招聘测试中对SMARCA5的推广者进行了评估.
功能性测试以确定SMAD结合基因的重要性.
评估TGF-β刺激和TGFBR1抑制对ciTRAN和病毒基因表达的影响.

主要成果:

艾滋病毒-1 Vpr诱导TGF-β的产生,导致前病毒性环RNA ciTRAN (编码由SMARCA5) 的上调.
在SMARCA5推广者中,SMAD2/3以Vpr依赖的方式被招募到SMARCA5中,这对于ciTRAN升级至关重要.
与QKI蛋白一起,TGF-β-SMAD信号通路调节着ciTRAN生物发生和SMARCA5mRNA的表达.
抑制TGFBR1可以降低Vpr介导的ciTRAN和病毒基因表达.

结论:

在HIV-1感染期间,TGF-β-SMAD轴在调节ciTRAN表达方面发挥着至关重要的作用.
通过TGF-β调节的ciTRAN上调可能会影响HIV-1复制.
准TGF-β信号通路提供了一个调节HIV-1复制的潜在策略.

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TGF - β Signaling Pathway

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...