需要SIRT-1才能释放包裹式肠道病毒
Alagie Jassey1, James Logue1, Stuart Weston1
1Department of Microbiology and Immunology and Center for Pathogen Research, University of Maryland, Baltimore, Baltimore, United States.
eLife
|October 18, 2023
概括
SIRT-1对肠道病毒D68 (EV-D68) 感染和释放至关重要. 这种基因组脱乙酶通过抑制内质网膜应激来促进病毒颗粒的释放,从而影响病毒标位.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 肠道病毒D68 (EV-D68) 是一种重新出现的病原体,导致呼吸系统疾病和急性状髓炎.
- 自和内质网膜 (ER) 压力是病毒感染中涉及的细胞过程.
- 特定宿主因子,如SIRT-1在EV-D68复制中的作用仍然不完全理解.
研究的目的:
- 为了研究质脱乙酶SIRT-1在EV-D68感染中的作用.
- 阐明SIRT-1影响病毒复制和释放的机制.
- 确定SIRT-1的前病毒性活性是否与其脱乙酶功能或自有关.
主要方法:
- 使用siRNA的SIRT-1敲击.
- 评估自流量和EV-D68病毒标位.
- 操纵ER压力通路 (thapsigargin治疗,SERCA2A敲击). 通过这种方法可以控制ER的压力通路.
- 分析病毒释放机制 (包裹与非包裹颗粒).
主要成果:
- 抑制SIRT-1 knockdown抑制了自和显著降低了EV-D68细胞外位数.
- SIRT-1的前病毒性活性独立于其脱乙酶功能和自性.
- SIRT-1抑制了ER压力,并诱导ER压力没有进一步影响SIRT-1淘汰细胞中的病毒标位.
- 通过SIRT-1 knockdown降低了脊髓灰质炎病毒和SARS-CoV-2的标位,但没有降低coxsackievirus B3.
- SIRT-1对于外EV-D68颗粒的释放至关重要,需要将其转移到细胞质中.
结论:
- 在EV-D68感染中,SIRT-1起着关键的前病毒性作用,主要是通过抑制ER压力.
- 该机制涉及SIRT-1的细胞转位,以促进包裹的EV-D68病毒的释放.
- SIRT-1的影响扩展到其他病毒,如小儿麻症病毒和SARS-CoV-2,这表明它在病毒病变发生过程中发挥了更广泛的作用.
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