疫苗病毒诱导了内质网膜应激,并通过ATF6α转录因子激活了未折叠的蛋白质反应
Thiago Lima Leão1, Karine Lima Lourenço1, Cid de Oliveira Queiroz1
1Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
Virology journal
|July 11, 2023
概括
疫苗病毒 (VACV) 通过激活ATF6α信号和降低IRE1α-XBP1的调节来操纵未折叠蛋白响应 (UPR),影响细胞应激反应和病毒复制.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 细胞应激反应对于宿主对病原体的防御至关重要.
- 疫苗病毒 (VACV),一个Poxviridae家族成员,采用策略来操纵宿主应激反应进行复制.
- 了解VACV与细胞应激通路的相互作用,例如展开蛋白质反应 (UPR),是关键.
研究的目的:
- 调查VACV病毒性 (WR) 和非病毒性 (MVA) 菌株对UPR的激活.
- 确定特定的UPR信号分支 (ATF6α和IRE1α-XBP1) 在VACV感染中的作用.
主要方法:
- 逆转录-聚合酶链反应限制片长多态化 (RT-PCR RFLP) 和定量PCR (qPCR) 来分析XBP1mRNA处理.
- 报告者基因测试以评估ATF6成分转位和转录活性.
- 在ATF6α-knockout小鼠胚胎纤维细胞 (MEFs) 中的病毒繁殖曲线.
主要成果:
- VACV感染导致XBP1mRNA处理的负调节.
- ATF6α转移到核中,并在感染细胞中显示出增加的转录活性.
- VACV WR菌株在ATF6α-Knockout MEF中显示病毒产量减少,这表明ATF6α对复制的重要性.
结论:
- VACV WR 和 MVA 菌株调节了 UPR 路径.
- 病毒感染通过ATF6α信号发送触发了内分泌网膜伴侣表达.
- 在感染过程中,VACV可以积极阻止IRE1α-XBP1的激活,同时强大激活ATF6α.
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