质子激活的化物通道抑制了SARS-CoV-2尖端蛋白介导的病毒通过内体通路进入
bioRxiv : the preprint server for biology
|March 31, 2025
概括
质子激活化物 (PAC) 通道通过调节内体酸性化,抑制SARS-CoV-2的进入. 过度表达的PAC阻断了病毒的进入,这表明它是SARS-CoV-2感染的潜在治疗标.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 通过与血管素转化酶2 (ACE2) 的相互作用进入宿主细胞.
- 细胞进入涉及内体酸性化,由V-ATPase质子和通过CLC载体进口离子 (Cl-) 调节.
- 质子激活化物 (PAC) 通道是一个最近发现的调节器,通过释放Cl-.
研究的目的:
- 调查质子激活化物 (PAC) 通道在SARS-CoV-2病毒进入中的作用.
- 为了确定PAC通道活动是否影响SARS-CoV-2感染的内体细胞路径.
主要方法:
- 在ACE2表达的HEK 293T细胞中过度表达PAC通道,以评估其对SARS-CoV-2伪病毒入口的影响.
- 评估PAC通道的内体位和通道活性与其抑制功能相关的评估.
- 在用甲素抑制剂 (E64-d) 和/或表达TMPRSS的细胞中对病毒进入抑制的评估2.
- 在过度表达PAC的Vero E6细胞中使用活的SARS-CoV-2分离物 (B.1和Omicron XBB.1.16) 进行斑块检测.
主要成果:
- 过度表达PAC通道显著抑制了SARS-CoV-2尖端介导的病毒进入ACE2表达细胞.
- 抑制作用取决于PAC的内体位和通道活性,并模仿了甲素抑制.
- 在Vero E6细胞中,PAC过度表达减少了B.1和Omicron XBB.1.16 SARS-CoV-2菌株的病毒斑块形成.
结论:
- 质子激活化物 (PAC) 通道在抑制SARS-CoV-2通过内体通路进入中发挥着关键作用.
- PAC通道活性是调节内体酸性化和限制病毒感染的关键因素.
- 该PAC道代表了对抗SARS-CoV-2和其他利用内体入口的病毒的潜在新型治疗标.
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