National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, Beijing, 100730, P.R. China.
Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, 100730, P.R. China.
Int J Biol Sci. 2024 Aug 1;20(11):4178-4189. doi: 10.7150/ijbs.95894. eCollection 2024.
Currently, chronic hepatitis B virus infection is still one of the most serious public health problems in the world. Though current strategies are effective in controlling infection and slowing down the disease process, it remains a big challenge to achieve a functional cure for chronic hepatitis B in a majority of patients due to the inability to clear the cccDNA pool. The mammalian target of rapamycin (mTOR) integrates nutrition, energy, growth factors, and other extracellular signals, participating in gene transcription, protein translation, ribosome synthesis, and other biological processes. Additionally, mTOR plays an extremely important role in cell growth, apoptosis, autophagy, and metabolism. More and more evidence show that HBV infection can activate the mTOR pathway, suggesting that HBV uses or hijacks the mTOR pathway to facilitate its own replication. Therefore, mTOR signaling pathway may be a key target for controlling HBV infection. However, the role of the central cytokine mTOR in the pathogenesis of HBV infection has not yet been systematically addressed. Notably, mTOR is commonly activated in hepatocellular carcinoma, which can progress from chronic hepatitis B. This review systematically summarizes the role of mTOR in the life cycle of HBV and its impact on the clinical progression of HBV infection.
目前,慢性乙型肝炎病毒感染仍然是全球最严重的公共卫生问题之一。尽管目前的治疗策略在控制感染和减缓疾病进程方面非常有效,但由于无法清除 cccDNA 池,大多数患者实现慢性乙型肝炎的功能性治愈仍然是一个巨大的挑战。哺乳动物雷帕霉素靶蛋白(mTOR)整合了营养、能量、生长因子和其他细胞外信号,参与基因转录、蛋白质翻译、核糖体合成和其他生物过程。此外,mTOR 在细胞生长、凋亡、自噬和代谢中发挥着极其重要的作用。越来越多的证据表明,HBV 感染可以激活 mTOR 途径,这表明 HBV 利用或劫持 mTOR 途径来促进自身复制。因此,mTOR 信号通路可能是控制 HBV 感染的关键靶点。然而,中央细胞因子 mTOR 在 HBV 感染发病机制中的作用尚未得到系统解决。值得注意的是,mTOR 在肝细胞癌中通常被激活,而肝细胞癌可以从慢性乙型肝炎进展而来。本综述系统总结了 mTOR 在 HBV 生命周期中的作用及其对 HBV 感染临床进展的影响。