ATF6-mediated mild ER stress inhibits HBV transcription and replication, which is dependent on mTOR activation

IF 2.8 3区医学 Q3 VIROLOGY

Virology Pub Date : 2025-02-06 DOI:10.1016/j.virol.2025.110448

Lin Lu , Ying Feng , Yucai Geng , Zhixiang Liu , Yan Wu , Chen Cai , Ji Zhang , Xingda Huang , Tongchun Xue , Bo Gao

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引用次数: 0

Abstract

Chronic hepatitis B (CHB) remains a serious global health problem. In our previous investigation, HBV was found to activate a mild ER stress, which facilitated the establishment of persistent HBV infection. However, the role of ER stress manipulation in HBV replication and its underlying mechanisms remain still unclear. Our data showed that mild ER stress inhibited HBV transcription and replication, while severe ER stress enhanced them. Mechanistically, in contrary to the effect on HBV replication, mild ER stress activated whereas severe ER stress inhibited mTOR signaling in HBV-infected cells. Further, mTOR signaling was revealed to be critical for mild ER stress-mediated HBV inhibition. Furthermore, ATF6 but not PERK or IRE1α was found to be involved in mild ER stress-mediated mTOR and the following HBV inhibition. Moreover, ATF6, per se, could inhibit HBV transcription and replication via activating mTOR signaling. Together, ATF6-mediated mild ER stress inhibited HBV transcription and replication through mTOR activation, which might present as an important therapeutic target for CHB patients.

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atf6介导的轻度内质网应激抑制HBV转录和复制，这依赖于mTOR的激活

慢性乙型肝炎（CHB）仍然是一个严重的全球卫生问题。在我们之前的研究中，发现HBV可以激活轻微的内质网应激，从而促进持续HBV感染的建立。然而，内质网应激在HBV复制中的作用及其潜在机制仍不清楚。我们的数据显示，轻度内质网应激抑制HBV的转录和复制，而重度内质网应激则增强HBV的转录和复制。在机制上，与对HBV复制的影响相反，轻度内质网应激激活HBV感染细胞，而严重内质网应激抑制mTOR信号传导。此外，mTOR信号对内质网应激介导的轻度HBV抑制至关重要。此外，发现ATF6而不是PERK或IRE1α参与轻度内质网应激介导的mTOR和随后的HBV抑制。此外，ATF6本身可以通过激活mTOR信号来抑制HBV的转录和复制。总之，atf6介导的轻度内质网应激通过mTOR激活抑制HBV转录和复制，这可能是CHB患者的一个重要治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virology 医学-病毒学

CiteScore

6.00

自引率

0.00%

发文量

157

审稿时长

50 days

期刊介绍： Launched in 1955, Virology is a broad and inclusive journal that welcomes submissions on all aspects of virology including plant, animal, microbial and human viruses. The journal publishes basic research as well as pre-clinical and clinical studies of vaccines, anti-viral drugs and their development, anti-viral therapies, and computational studies of virus infections. Any submission that is of broad interest to the community of virologists/vaccinologists and reporting scientifically accurate and valuable research will be considered for publication, including negative findings and multidisciplinary work.Virology is open to reviews, research manuscripts, short communication, registered reports as well as follow-up manuscripts.