Transcriptional Regulation of Antiviral Interferon-Stimulated Genes

Wang, Wenshi; Xu, Lei; Su, Junhong; Peppelenbosch, Maikel P.; Pan, Qiuwei

doi:10.1016/j.tim.2017.01.001

Cited by 161 publications

(136 citation statements)

References 132 publications

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“…Induction of ISGs is the hallmark of STAT1 activation [30]. As expected, a subset of ISGs were strongly induced by IFN-α treatment, while the stimulation was abolished in STAT1 knockout cells (Fig.…”

Section: Resultssupporting

confidence: 63%

Dichotomal functions of phosphorylated and unphosphorylated STAT1 in hepatocellular carcinoma

Chen

Liu

et al. 2018

J Mol Med

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Interferons (IFNs) with antiviral and immune-stimulatory functions have been widely used in prevention and treatment of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 1 (STAT1) is a key element of the IFN signaling, and the function of STAT1 is critically determined by its phosphorylation state. This study aims to understand the functions of phosphorylated (p-) and unphosphorylated (u-) STAT1 in HCC. We found that u-STAT1 is significantly elevated in patient HCC tumor tissues and predominantly expressed in cytoplasm; while p-STAT1 is absent. Loss of u-STAT1 potently arrested cell cycle and inhibited cell growth in HCC cells. Induction of p-STAT1 by IFN-α treatment effectively triggers the expression of interferon-stimulated genes (ISGs), but has moderate effect on HCC cell growth. Interestingly, both u-STAT1 and p-STAT1 are induced by IFN-α, through with distinct time-dependent process. Furthermore, the ISG induction patterns mediated by p-STAT1 and u-STAT1 are also distinct. Importantly, artificial blocking of the induction of u-STAT1, but not p-STAT1, sensitizes HCC cells to treatment of IFNs. Therefore, p-STAT1 and u-STAT1 exert dichotomal functions and coordinately regulate the responsiveness to IFN treatment in HCC.Key Messages STAT1 is upregulated and predominantly presented as u-STAT1 in HCC, while p-STAT1 is absent.U-STAT1 sustains but p-STAT1 inhibits HCC growth.The dynamic change of phosphorylation state of STAT1 control the responsiveness to IFN treatment. Electronic supplementary materialThe online version of this article (10.1007/s00109-018-1717-7) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 63%

Dichotomal functions of phosphorylated and unphosphorylated STAT1 in hepatocellular carcinoma

Chen

Liu

et al. 2018

J Mol Med

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“…Upon IFN production, the released IFN molecules bind to cell‐surface receptors and initiate signal transduction prominently through the JAK–STAT pathway. This activates the transcription of hundreds of ISGs that are the effectors of cell‐autonomous antiviral defense . Transfection of HEV RNA in U3A cells (which are STAT1‐deficient) or U6A cells (which are STAT2‐deficient) achieved much lower expression levels of ISGs compared with WT (Fig.…”

Section: Resultsmentioning

confidence: 96%

The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response

Wang

et al. 2018

Hepatology

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HEV infection elicits an active IFN-related antiviral response in vitro and in patients, triggered by the viral RNA and mediated by IFN regulatory factors 3 and 7 and the Janus kinase-signal transducer and activator of transcription cascade; these findings have revealed new insights into HEV-host interactions and provided the basis for understanding the pathogenesis and outcome of HEV infection. (Hepatology 2018;67:2096-2112).

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“…The early and non‐specific detection of hepatitis viruses is generally through the recognition by pathogen‐associated molecular patterns (PAMP) as innate immunity sensors. This leads to the activation of downstream IFN signal pathway and subsequent production of the ultimate antiviral effectors, interferon‐stimulated genes (ISG) . MAVS, acting as an adaptor for transcription and production of IFN, shows specific interactions with different hepatitis viruses.…”

Section: The Mutual Interactions Between Hepatitis Viruses and Mitochmentioning

confidence: 99%

Mitochondria in the biology, pathogenesis, and treatment of hepatitis virus infections

Zhang

et al. 2019

Reviews in Medical Virology

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Summary Hepatitis virus infections affect a large proportion of the global population. The host responds rapidly to viral infection by orchestrating a variety of cellular machineries, in particular, the mitochondrial compartment. Mitochondria actively regulate viral infections through modulation of the cellular innate immunity and reprogramming of metabolism. In turn, hepatitis viruses are able to modulate the morphodynamics and functions of mitochondria, but the mode of actions are distinct with respect to different types of hepatitis viruses. The resulting mutual interactions between viruses and mitochondria partially explain the clinical presentation of viral hepatitis, influence the response to antiviral treatment, and offer rational avenues for novel therapy. In this review, we aim to consider in depth the multifaceted interactions of mitochondria with hepatitis virus infections and emphasize the implications for understanding pathogenesis and advancing therapeutic development.

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Transcriptional Regulation of Antiviral Interferon-Stimulated Genes

Cited by 161 publications

References 132 publications

Dichotomal functions of phosphorylated and unphosphorylated STAT1 in hepatocellular carcinoma

Dichotomal functions of phosphorylated and unphosphorylated STAT1 in hepatocellular carcinoma

The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response

Mitochondria in the biology, pathogenesis, and treatment of hepatitis virus infections

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