Orchestration of intracellular circuits by g protein-coupled receptor 39 for hepatitis b virus proliferation

Kaku Goto, Hironori Nishitsuji, Masaya Sugiyama, Nao Nishida, Masashi Mizokami, Kunitada Shimotohno

研究成果: Article査読

1 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号5661
ページ(範囲)1-16
ページ数16
ジャーナルInternational journal of molecular sciences
21
16
DOI
出版ステータスPublished - 02-08-2020
外部発表はい

All Science Journal Classification (ASJC) codes

  • 触媒
  • 分子生物学
  • 分光学
  • コンピュータ サイエンスの応用
  • 物理化学および理論化学
  • 有機化学
  • 無機化学

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