病毒编码的插白素-6 (vIL-6) 与人类IL-6协调,在KSHV感染期间调节细胞因子表达
Yahaira Bermudez1, Samantha Schultz1,2, Jacob Miles1
1Department of Microbiology, University of Massachusetts, Amherst, USA.
bioRxiv : the preprint server for biology
|November 19, 2025
概括
卡波西肉瘤相关疹病毒 (KSHV) 感染涉及病毒性介质素-6 (vIL-6) 和宿主介质素-6 (IL-6). 它们的联合作用增强了免疫调节,促进了KSHV的持久性和疾病.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 卡波西肉瘤相关疹病毒 (KSHV) 导致终身感染,往往导致免疫功能低下的人患病.
- KSHV操纵宿主基因表达,特别是通过病毒SOX酶诱导RNA衰变,但一些宿主转录物如Interleukin-6 (IL-6) 逃避降解.
- KSHV编码了IL-6的功能性病毒同类物,称为病毒IL-6 (vIL-6),其调节对病毒病原性至关重要.
研究的目的:
- 研究KSHV感染期间vIL-6表达的调节机制.
- 阐明vIL-6和宿主IL-6在调节宿主基因表达,炎症信号和KSHV病变发生中的不同和协同作用.
主要方法:
- 在KSHV感染细胞中使用vIL-6无突变体和IL-6 Knockdown进行转录组分析.
- 评估vIL-6和IL-6对宿主基因表达和炎症通路的贡献.
- 功能测试评估vIL-6的信号传输能力,包括JAK/STAT通路激活.
主要成果:
- 与宿主IL-6不同,vIL-6mRNA通过明显的转录调节来逃避SOX介导的衰变.
- 由于vIL-6和/或IL-6的耗尽,导致宿主基因表达的差异性变化,影响化学激素信号通路.
- 当vIL-6和IL-6都存在时,观察到对宿主基因表达的协同效应.
- 单靠vIL-6就足以激活关键的促炎信号通路,包括JAK/STAT.
结论:
- vIL-6和宿主IL-6表现出一种机械协同作用,可以放大KSHV介导的免疫调节.
- 这种协同作用可能有助于病毒的持久性和KSHV相关瘤发生的发展.
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