牛痘病毒通过 ATF6α 转录因子诱导内质网应激并激活未折叠蛋白反应。
Vaccinia virus induces endoplasmic reticulum stress and activates unfolded protein responses through the ATF6α transcription factor.
机构信息
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
出版信息
Virol J. 2023 Jul 11;20(1):145. doi: 10.1186/s12985-023-02122-y.
BACKGROUND
Cell responses to different stress inducers are efficient mechanisms that prevent and fight the accumulation of harmful macromolecules in the cells and also reinforce the defenses of the host against pathogens. Vaccinia virus (VACV) is an enveloped, DNA virus, belonging to the Poxviridae family. Members of this family have evolved numerous strategies to manipulate host responses to stress controlling cell survival and enhancing their replicative success. In this study, we investigated the activation of the response signaling to malformed proteins (UPR) by the VACV virulent strain-Western Reserve (WR)-or the non-virulent strain-Modified Vaccinia Ankara (MVA).
METHODS
Through RT-PCR RFLP and qPCR assays, we detected negative regulation of XBP1 mRNA processing in VACV-infected cells. On the other hand, through assays of reporter genes for the ATF6 component, we observed its translocation to the nucleus of infected cells and a robust increase in its transcriptional activity, which seems to be important for virus replication. WR strain single-cycle viral multiplication curves in ATF6α-knockout MEFs showed reduced viral yield.
RESULTS
We observed that VACV WR and MVA strains modulate the UPR pathway, triggering the expression of endoplasmic reticulum chaperones through ATF6α signaling while preventing IRE1α-XBP1 activation.
CONCLUSIONS
The ATF6α sensor is robustly activated during infection while the IRE1α-XBP1 branch is down-regulated.
背景
细胞对不同应激诱导剂的反应是有效的机制，可防止和抵抗细胞内有害大分子的积累，增强宿主对病原体的防御能力。牛痘病毒（VACV）是一种包膜 DNA 病毒，属于痘病毒科。该家族的成员已经进化出许多策略来操纵宿主对压力的反应，控制细胞存活并增强其复制成功。在这项研究中，我们研究了 VACV 强毒株-Western Reserve（WR）或非致毒株-Modified Vaccinia Ankara（MVA）对错误折叠蛋白反应（UPR）信号的激活。
方法
通过 RT-PCR RFLP 和 qPCR 检测，我们检测到 VACV 感染细胞中 XBP1 mRNA 加工的负调控。另一方面，通过 ATF6 成分报告基因检测，我们观察到其易位到感染细胞的核内，并观察到其转录活性的显著增加，这似乎对病毒复制很重要。在 ATF6α 敲除 MEFs 中，WR 株单周期病毒增殖曲线显示病毒产量减少。
结果
我们观察到 VACV WR 和 MVA 株调节 UPR 途径，通过 ATF6α 信号触发内质网伴侣蛋白的表达，同时抑制 IRE1α-XBP1 的激活。
结论
在感染过程中，ATF6α 传感器被强烈激活，而 IRE1α-XBP1 分支被下调。
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