在HIV-1细胞对细胞传播期间,CARD8炎症酶的激活
Jessie Kulsuptrakul1,2, Michael Emerman2, Patrick S Mitchell3,4
1Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195, USA.
bioRxiv : the preprint server for biology
|September 4, 2024
概括
在细胞间传播过程中,CARD8检测HIV-1蛋白酶活性,从而激活炎症酶. 艾滋病毒蛋白酶的变异会影响这种天生的免疫感知和炎症.
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:
- CARD8 (Caspase-recruitment域家族成员8) 识别了HIV-1蛋白酶的活性.
- 艾滋病毒-1蛋白酶切割了CARD8的N端模仿基因,引发了炎症酶激活.
- 了解CARD8在HIV-1细胞间传播中的作用对于先天性免疫研究至关重要.
研究的目的:
- 通过病毒突触通过HIV-1细胞间传播期间研究CARD8炎症酶激活.
- 确定艾滋病毒蛋白酶活性和CARD8感应变化的作用.
- 在这种情况下,评估NLRP3炎症酶的贡献.
主要方法:
- 在HIV-1细胞转移期间研究了初级人类单细胞衍生的巨细胞中的CARD8炎症酶激活.
- 利用HIV-1蛋白酶抑制剂耐药克隆来分析CARD8感应的病毒决定因素.
- 评估了对野生型和突变HIV-1蛋白酶的反应中的CARD8激活.
主要成果:
- 艾滋病毒-1细胞对细胞的传播强烈诱导CARD8炎症酶激活.
- 这种激活依赖于HIV蛋白酶活性,但在很大程度上独立于NLRP3炎症酶.
- 与野生类型相比,突变的HIV-1蛋白酶表现出不同的CARD8分裂和激活.
结论:
- 在细胞间传播过程中,CARD8感知HIV-1蛋白酶活性.
- 艾滋病毒-1蛋白酶变异影响病毒多蛋白处理和先天免疫传感.
- 这些发现凸显了病毒蛋白酶进化的对宿主炎症反应的影响.
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