ARF6是SARS-CoV-2感染的宿主因子体外
C Mirabelli1,2, J Bragazzi Cunha3, J W Wotring4
1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
The Journal of general virology
|June 21, 2023
概括
严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 进入细胞的依赖于胆固醇,而不是动氨酸. 抑制ADP-ribosylation因子6 (ARF6) 减少病毒感染,这表明ARF6是潜在的抗病毒标.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 利用ACE2和其他因素进入细胞,主要是通过血融合或内细胞分裂.
- 与直接融合相比,通过内细胞通路进入病毒的理解仍然较少.
- 诸如ADP-ribosylation factor 6 (ARF6) 这样的宿主因素与病毒复制和感染有关.
研究的目的:
- 为了研究SARS-CoV-2通过内细胞通路进入的机制.
- 评估动氨酸和胆固醇在SARS-CoV-2内细胞分裂中的作用.
- 评估ADP-ribosylation factor 6 (ARF6) 作为潜在的宿主因子和SARS-CoV-2感染的治疗标.
主要方法:
- 利用抗卡莫斯塔特的Huh-7细胞,独立于TMPRSS2.2研究SARS-CoV-2的进入.
- 采用CRISPR/Cas9遗传删除来评估ARF6对病毒吸收和感染的影响.
- 在细胞系和有机体模型中使用NAV-2729进行ARF6的药理抑制.
主要成果:
- 发现SARS-CoV-2进入Huh-7细胞是依赖胆固醇的,而不是依赖动氨酸的.
- 通过CRISPR/Cas9调节的ARF6删除导致SARS-CoV-2吸收和感染的适度减少.
- 通过NAV-2729对ARF6的药理抑制表明,病毒感染在细胞系和器官上有剂量依赖的减少.
结论:
- 胆固醇在SARS-CoV-2的内细胞进入中发挥着重要作用.
- ADP-ribosylation factor 6 (ARF6) 是SARS-CoV-2复制和感染在各种细胞环境中的关键宿主因子.
- 用像NAV-2729这样的抑制剂向ARF6是一个有希望的抗病毒策略来对抗SARS-CoV-2.
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