BACH2驱动的组织内存程序促进了HIV-1的持续性
Yulong Wei1, Haocong Katherine Ma1, Michelle E Wong1
1Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06519, USA.
bioRxiv : the preprint server for biology
|January 7, 2025
概括
转录抑制剂BACH2通过在肠道中产生长寿记忆T细胞来促进HIV-1的持久性. 向BACH2可能为HIV-1感染提供新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 转录抑制剂BACH2影响T细胞分化和记忆形成.
- 艾滋病毒-1 确立了肠道内特定T细胞子集的持久性.
研究的目的:
- 研究BACH2在肠道CD4+T细胞内HIV-1持久性中的作用.
- 确定BACH2作为HIV-1持久性的潜在治疗点.
主要方法:
- 结合单细胞DOGMA-seq和TREK-seq来分析100,744个肠道T细胞中的染色质可访问性,转录组,表面蛋白质,T细胞受体,HIV-1 DNA和RNA.
- 比较来自AVIREMICHIV-1+个体和HIV-1捐赠者的细胞.
- 在体外对肠道CD4+T细胞进行了感染.
主要成果:
- BACH2将肠道组织的T细胞 (TRM) 塑造为具有减少效应因子功能的长寿命记忆细胞.
- 感染HIV-1的细胞富含TRM (80.8%),并显示增加了BACH2的可访问性,TRM/生存基因表达和Th17极化.
- 在体外研究表明,偏好的HIV-1感染和持久性在CCR6+TRMs.
结论:
- 由BACH2驱动的TRM计划促进了HIV-1在肠道中的持久性.
- BACH2代表了一种用于控制HIV-1持续性的新疗法标.
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