G蛋白偶聯受體39對乙型肝炎病毒增殖的細胞內迴路的編排

StephenW

Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation
Kaku Goto  1 , Hironori Nishitsuji  1 , Masaya Sugiyama  1 , Nao Nishida  1 , Masashi Mizokami  1 , Kunitada Shimotohno  1
Affiliations
Affiliation

    1
    Genome Medical Science Project, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516, Japan.

    PMID: 32784555 DOI: 10.3390/ijms21165661

Abstract

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.

Keywords: CEBPB; GLI; GPR39; HBV; HCC; HSP.
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StephenW

G蛋白偶聯受體39對乙型肝炎病毒增殖的細胞內迴路的編排
後藤角1，西廣紀郎1，杉山雅矢1，西田直夫1，宮政雅密1，下田信田1
隸屬關係
聯繫

    1個
    日本千葉市市川市國立全球健康與醫學中心肝炎和免疫學研究中心基因組醫學科學項目，日本千葉市272-8516。

    PMID：32784555 DOI：10.3390 / ijms21165661

抽象

乙型肝炎病毒（HBV）是引起肝細胞癌（HCC）的高度持久性病原體，可充分利用宿主機制，提供治療靶點。在這裡，我們旨在使用我們最近生成的報告者HBV鑑定新型可藥物治療的宿主細胞因子。在G蛋白偶聯受體（GPCR）的RNAi篩選中，GPCR39（GPR39）作為促進HBV增殖的首選。活性GPR39蛋白的慢病毒過表達和激動劑可增強病毒啟動子的HBV複製和轉錄活性，從而誘導CCAAT /增強子結合蛋白（CEBP）-β（CEBPB）的表達。同時，發現GPR39激活熱休克反應，上調前病毒熱休克蛋白（HSPs）的表達。另外，神經膠質瘤相關的癌基因同源信號，最近報導的GPR39靶標，被建議抑制HBV複製並最終抑制CEBPB和HSPs的表達。因此，GPR39前病毒控制細胞內電路，同時影響致癌基因的功能。 GPR39和受調控的信號網絡將作為抗病毒靶標，具有GPR39功能選擇性抑製劑的策略可以開發針對宿主的抗病毒療法，預防HCC。

關鍵字：CEBPB； GLI； GPR39；乙肝病毒HCC； HSP。

StephenW

https://www.mdpi.com/1422-0067/21/16/5661/pdf