瘤坏死因子-阿尔法抑制患者衍生的原型BK多瘤病毒的复制,同时激活重新排列的菌株.
Lise Lauterbach-Rivière1, Lucia Thuringer1,2, Pascal Feld1
1Institute of Virology, Saarland University Medical Center, Homburg, Germany.
Journal of medical virology
|February 14, 2025
概括
瘤坏死因子-α (TNF-α) 根据其遗传类型对BK多瘤病毒 (BKPyV) 有不同的影响. TNF-α增强了重新排列的BKPyV复制,但抑制了原型BKPyV,影响了移植结果.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 腎臟病學 (nephrology) 是一種醫學.
背景情况:
- BK多瘤病毒 (BKPyV) 的重新激活会导致移植接受者的显著病.
- 目前还没有批准的药物用于BKPyV的重新激活.
- 瘤亡因子-α (TNF-α) 阻断是一种潜在的治疗方法,但其对BKPyV原型的影响尚不清楚.
研究的目的:
- 研究TNF-α对不同BKPyV原型的影响.
- 了解TNF-α对BKPyV复制的影响背后的机制.
- 为测试BKPyV疗法建立可靠的测试方法.
主要方法:
- 优化细胞培养用于野生类型 (ww) BKPyV. 强大的复制.
- 利用了原发性近管上皮细胞 (RPTEC) 和来自患者的BKPyV菌株.
- 在机械分析中使用siRNAs,嵌合体和突变的BKPyV菌株.
主要成果:
- TNF-α促进了重新排列的 (rr) BKPyV的复制,但抑制了野生型的 (ww) BKPyV.
- 干扰素- (IFN-γ) 抑制了BKPyV复制,即使存在TNF-α.
- TNF-α对rr-BKPyV复制的影响是由NF-κB p65途径介导的,而不是保留的NF-κB结合部位.
结论:
- 在移植患者中,TNF-α阻断可能会阻碍原型感染的自然抗BKPyV控制.
- 损坏的TH1反应可能会使TNF-α阻断有害.
- 炎症可能会选择耐受TNF-α抑制的BKPyV变体,突出显示在药物发现中需要临床相关的BKPyV分离物.
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