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Article

Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation

Genome Medical Science Project, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516, Japan
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(16), 5661; https://doi.org/10.3390/ijms21165661
Received: 13 July 2020 / Revised: 4 August 2020 / Accepted: 5 August 2020 / Published: 7 August 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Hepatitis B virus (HBV), a highly persistent pathogen causing hepatocellular carcinoma (HCC), takes full advantage of host machinery, presenting therapeutic targets. Here we aimed to identify novel druggable host cellular factors using the reporter HBV we have recently generated. In an RNAi screen of G protein-coupled receptors (GPCRs), GPCR39 (GPR39) appeared as the top hit to facilitate HBV proliferation. Lentiviral overexpression of active GPR39 proteins and an agonist enhanced HBV replication and transcriptional activities of viral promoters, inducing the expression of CCAAT/enhancer binding protein (CEBP)-β (CEBPB). Meanwhile, GPR39 was uncovered to activate the heat shock response, upregulating the expression of proviral heat shock proteins (HSPs). In addition, glioma-associated oncogene homologue signaling, a recently reported target of GPR39, was suggested to inhibit HBV replication and eventually suppress expression of CEBPB and HSPs. Thus, GPR39 provirally governed intracellular circuits simultaneously affecting the carcinopathogenetic gene functions. GPR39 and the regulated signaling networks would serve as antiviral targets, and strategies with selective inhibitors of GPR39 functions can develop host-targeted antiviral therapies preventing HCC. View Full-Text
Keywords: GPR39; HBV; HCC; HSP; CEBPB; GLI GPR39; HBV; HCC; HSP; CEBPB; GLI
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MDPI and ACS Style

Goto, K.; Nishitsuji, H.; Sugiyama, M.; Nishida, N.; Mizokami, M.; Shimotohno, K. Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation. Int. J. Mol. Sci. 2020, 21, 5661. https://doi.org/10.3390/ijms21165661

AMA Style

Goto K, Nishitsuji H, Sugiyama M, Nishida N, Mizokami M, Shimotohno K. Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation. International Journal of Molecular Sciences. 2020; 21(16):5661. https://doi.org/10.3390/ijms21165661

Chicago/Turabian Style

Goto, Kaku, Hironori Nishitsuji, Masaya Sugiyama, Nao Nishida, Masashi Mizokami, and Kunitada Shimotohno. 2020. "Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation" International Journal of Molecular Sciences 21, no. 16: 5661. https://doi.org/10.3390/ijms21165661

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