MTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication

Overview

Journal Virol Sin

Specialty Microbiology

Date 2021 Sep 28

PMID 34580816

Citations 11

Authors

Xueyu Wang

Zhiqiang Wei

Yongfang Jiang

Zhongji Meng

Mengji Lu

Affiliations

Soon will be listed here.

Abstract

Mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that includes mTOR complex (mTORC) 1 and mTORC2. The mTOR pathway is activated in viral hepatitis, including hepatitis B virus (HBV) infection-induced hepatitis. Currently, chronic HBV infection remains one of the most serious public health issues worldwide. The unavailability of effective therapeutic strategies for HBV suggests that clarification of the pathogenesis of HBV infection is urgently required. Increasing evidence has shown that HBV infection can activate the mTOR pathway, indicating that HBV utilizes or hijacks the mTOR pathway to benefit its own replication. Therefore, the mTOR signaling pathway might be a crucial target for controlling HBV infection. Here, we summarize and discuss the latest findings from model biology research regarding the interaction between the mTOR signaling pathway and HBV replication.

Citing Articles

The endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 3 attenuates the unfolded protein response and has pro-survival and pro-viral roles in hepatoma cells and hepatocellular carcinoma patients.

Ghionescu A, Uta M, Sorop A, Lazar C, Flintoaca-Alexandru P, Chiritoiu G J Biomed Sci. 2025; 32(1):11.

PMID: 39838427 PMC: 11752926. DOI: 10.1186/s12929-024-01103-9.

mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.

Mei L, Sun H, Yan Y, Ji H, Su Q, Chang L Int J Biol Sci. 2024; 20(11):4178-4189.

PMID: 39247820 PMC: 11379076. DOI: 10.7150/ijbs.95894.

SOD1 inhibition enhances sorafenib efficacy in HBV-related hepatocellular carcinoma by modulating PI3K/Akt/mTOR pathway and ROS-mediated cell death.

Lee J, Kim J, Lee R, Lee E, An H, Kwon Y J Cell Mol Med. 2024; 28(14):e18533.

PMID: 39034442 PMC: 11260765. DOI: 10.1111/jcmm.18533.

The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways.

Artimovic P, Spakova I, Macejkova E, Pribulova T, Rabajdova M, Marekova M Genes Immun. 2024; 25(4):277-296.

PMID: 38909168 PMC: 11327111. DOI: 10.1038/s41435-024-00283-6.

Interconnection of cellular autophagy and endosomal vesicle trafficking and its role in hepatitis B virus replication and release.

Li J, Lin Y, Wang X, Lu M Virol Sin. 2024; 39(1):24-30.

PMID: 38211880 PMC: 10877419. DOI: 10.1016/j.virs.2024.01.001.

References

Guo Z, Cheng X, Feng X, Zhao K, Zhang M, Yao R . The mTORC1/4EBP1/PPARγ Axis Mediates Insulin-Induced Lipogenesis by Regulating Lipogenic Gene Expression in Bovine Mammary Epithelial Cells. J Agric Food Chem. 2019; 67(21):6007-6018. DOI: 10.1021/acs.jafc.9b01411. View

Bossler F, Hoppe-Seyler K, Hoppe-Seyler F . PI3K/AKT/mTOR Signaling Regulates the Virus/Host Cell Crosstalk in HPV-Positive Cervical Cancer Cells. Int J Mol Sci. 2019; 20(9). PMC: 6539191. DOI: 10.3390/ijms20092188. View

Wang X, Lin Y, Liu S, Zhu Y, Lu K, Broering R . O-GlcNAcylation modulates HBV replication through regulating cellular autophagy at multiple levels. FASEB J. 2020; 34(11):14473-14489. DOI: 10.1096/fj.202001168RR. View

Weichhart T, Hengstschlager M, Linke M . Regulation of innate immune cell function by mTOR. Nat Rev Immunol. 2015; 15(10):599-614. PMC: 6095456. DOI: 10.1038/nri3901. View

Wang X, Lin Y, Kemper T, Chen J, Yuan Z, Liu S . AMPK and Akt/mTOR signalling pathways participate in glucose-mediated regulation of hepatitis B virus replication and cellular autophagy. Cell Microbiol. 2019; 22(2):e13131. DOI: 10.1111/cmi.13131. View

Liang T, Block T, McMahon B, Ghany M, Urban S, Guo J . Present and future therapies of hepatitis B: From discovery to cure. Hepatology. 2015; 62(6):1893-908. PMC: 4681668. DOI: 10.1002/hep.28025. View

Wang H, Wu H, Chen C, Fausto N, Lei H, Su I . Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress. Am J Pathol. 2003; 163(6):2441-9. PMC: 1892360. DOI: 10.1016/S0002-9440(10)63599-7. View

Laplante M, Sabatini D . mTOR signaling in growth control and disease. Cell. 2012; 149(2):274-93. PMC: 3331679. DOI: 10.1016/j.cell.2012.03.017. View

Shlomai A, Shaul Y . The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription. Biochem Biophys Res Commun. 2009; 381(4):544-8. DOI: 10.1016/j.bbrc.2009.02.078. View

10.

Tian Y, Sir D, Kuo C, Ann D, Ou J . Autophagy required for hepatitis B virus replication in transgenic mice. J Virol. 2011; 85(24):13453-6. PMC: 3233133. DOI: 10.1128/JVI.06064-11. View

11.

Zhou J, Tan S, Nicolas V, Bauvy C, Yang N, Zhang J . Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion. Cell Res. 2013; 23(4):508-23. PMC: 3616426. DOI: 10.1038/cr.2013.11. View

12.

Glebe D, Bremer C . The molecular virology of hepatitis B virus. Semin Liver Dis. 2013; 33(2):103-12. DOI: 10.1055/s-0033-1345717. View

13.

Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X . TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 2006; 126(5):955-68. DOI: 10.1016/j.cell.2006.06.055. View

14.

Tarn C, Lee S, Hu Y, Ashendel C, Andrisani O . Hepatitis B virus X protein differentially activates RAS-RAF-MAPK and JNK pathways in X-transforming versus non-transforming AML12 hepatocytes. J Biol Chem. 2001; 276(37):34671-80. DOI: 10.1074/jbc.M104105200. View

15.

Liu H, Xu J, Zhou L, Yun X, Chen L, Wang S . Hepatitis B virus large surface antigen promotes liver carcinogenesis by activating the Src/PI3K/Akt pathway. Cancer Res. 2011; 71(24):7547-57. DOI: 10.1158/0008-5472.CAN-11-2260. View

16.

Lee D, Kuo H, Chen C, Hsu J, Chou C, Wei Y . IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell. 2007; 130(3):440-55. DOI: 10.1016/j.cell.2007.05.058. View

17.

Wang B, Ducker G, Barczak A, Barbeau R, Erle D, Shokat K . The mammalian target of rapamycin regulates cholesterol biosynthetic gene expression and exhibits a rapamycin-resistant transcriptional profile. Proc Natl Acad Sci U S A. 2011; 108(37):15201-6. PMC: 3174577. DOI: 10.1073/pnas.1103746108. View

18.

Sengupta S, Peterson T, Laplante M, Oh S, Sabatini D . mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature. 2010; 468(7327):1100-4. DOI: 10.1038/nature09584. View

19.

Shin H, Park Y, Kim S, Moon H, Park D, Han Y . Hepatitis B virus X protein regulates hepatic glucose homeostasis via activation of inducible nitric oxide synthase. J Biol Chem. 2011; 286(34):29872-81. PMC: 3191028. DOI: 10.1074/jbc.M111.259978. View

20.

Yen C, Lin Y, Yen C, Tsai H, Tsai T, Chang K . Hepatitis B virus X protein upregulates mTOR signaling through IKKβ to increase cell proliferation and VEGF production in hepatocellular carcinoma. PLoS One. 2012; 7(7):e41931. PMC: 3407061. DOI: 10.1371/journal.pone.0041931. View