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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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.