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通过JCPyV对血液脑脊髓液屏障的高度限制性和定向性透

Bethany A O'Hara¹, Avraham S Lukacher¹, Kaitlin Garabian¹

¹Department of Cell Biology, Biochemistry, and Molecular Biology, The Warren Alpert Medical School, Brown University, Providence, Rhode Island, United States of America.

|July 22, 2024

概括

人类多重瘤病毒JCPyV可以入侵中枢神经系统. 研究人员发现,JCPyV通过转细胞和感染后的定向释放穿过血液-脑脊液屏障,可能导致神经疾病.

科学领域:

神经病毒学神经病毒学
细胞生物学细胞生物学

背景情况:

人类多重瘤病毒JCPyV感染了全球60%以上的人口.
在中枢神经系统入侵后,JCPyV会在免疫抑制的个体中引起致命的脱髓化疾病.
JCPyV神经入侵的机制尚不清楚,假设冠状动脉是其中的一条路线.

研究的目的:

为了研究状作为JCPyV神经侵袭的场所.
通过使用人类冠状动脉上皮质细胞来建模血液-脑脊液 (B-CSF) 屏障.

主要方法:

使用成年人状结质上皮细胞的跨井系统来建模B-CSF屏障.
使用自由病毒和细胞外囊泡 (EVJC+) 评估病毒透率.
通过使用宏皮诺细胞体的抑制剂,克拉特林依赖转细胞体,依赖转细胞体和P-gp,MRP2,BCRP多药物耐药性转运体的运输机制进行了研究.

主要成果:

胸膜上皮细胞形成了一个高度限制性的B-CSF屏障.
少量的JCPyV和EVJC+穿透了屏障,感染了星球细胞.
在JCPyV中,用于入口的巨型皮诺细胞体和用于基底侧到顶端运输的克拉特林/浮板依赖转细胞体.
感染导致传染性病毒的定向释放到峰 (CSF) 腔室.

结论:

冠状交叉体作为一种限制性屏障,但允许JCPyV通过直接转细胞化透.
冠状动脉细胞的JCPyV感染导致向性释放到CSF,从而导致神经侵入.
确定了JCPyV通过B-CSF屏障进入和释放的独特机制.

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