肝 X 受体诱导宿主 E3 联酶 IDOL 准人类细胞巨病毒重新激活的决定因素
Luwanika Mlera1,2, Donna Collins-McMillen1,2, Sebastian Zeltzer1,2
1Department of Immunobiology, University of Arizona, Tucson, Arizona, USA.
Journal of virology
|June 20, 2023
概括
细胞E3酶IDOL针对人类细胞巨血病毒 (HCMV) UL136p33进行降解,这是建立病毒延迟的关键步骤. 这种宿主病毒相互作用调节HCMVV.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 疹病毒,包括人类细胞巨血病毒 (HCMV),建立终身潜伏感染.
- 延迟会带来严重的疾病风险,特别是在免疫受损的个体中.
- 控制HCMV潜伏和重新激活的机制对于疾病控制至关重要.
研究的目的:
- 阐明肝X受体 (LXR) 信号限制病毒复制的机制.
- 为了确定参与调节人类细胞巨核病毒 (HCMV) 延迟和重新激活的宿主因素.
- 调查E3结合酶IDOL在控制HCMVUL136p33稳定性和病毒生命周期中的作用.
主要方法:
- 研究了细胞E3结合酶IDOL和HCMVUL136p33蛋白之间的相互作用.
- 利用蛋白质体降解试验和位点定向突变发生法来研究UL136p33的稳定性.
- 检查了血液细胞中的IDOL表达及其与HCMV延迟和分化的相关性.
- 评估了IDOL淘汰和LXR信号诱导对HCMV复制和重新激活的影响.
主要成果:
- 细胞E3结合酶IDOL针对HCMVUL136p33蛋白进行蛋白质酶体降解.
- 通过突变稳定UL136p33,可以防止病毒复制延迟所需的病毒复制沉默.
- 在未分化的细胞中,IDOL的表达率很高 (HCMV延迟),在分化 (重新激活刺激) 后会降低.
- Knockdown 的 IDOL 影响病毒基因表达在 WT HCMV 感染,但不是与稳定 UL136p33.3.
- LXR信号限制了WT HCMV的重新激活,但不是稳定UL136p33.3的病毒.
结论:
- UL136p33-IDOL相互作用是HCMV延迟和重新激活之间的切换的关键调节器.
- HCMV UL136p33稳定性,由宿主E3结合酶IDOL控制,作为宿主条件的传感器.
- 这种宿主病毒相互作用允许HCMV在维持延迟或启动复制之间进行导航决策.
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