STING signaling activation inhibits HBV replication and attenuates the severity of liver injury and HBV-induced fibrosis

Li, Yuqi; He, Minjing; Wang, Ziyu; Duan, Zhiyun; Guo, Zhiwei; Wang, Ziteng; Gong, Ruijie; Chu, Tianhao; Cai, Jia‐Bin; Gao, Bo

doi:10.1038/s41423-021-00801-w

Cited by 40 publications

(43 citation statements)

References 86 publications

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“…In particular, after cytoplasmic DNA is activated by cGAS or DAI, these molecules can induce the activation of the stimulator of interferon genes (STING) to further induce the expression of IFN and inflammatory cytokines (8,165). It has been found that the cGAS-STING pathway facilitates the inhibition of HBV replication and attenuates hepatocyte injury and fibrosis induced by the virus (166)(167)(168). However, the expression levels of cGAS and its effector genes have been shown to decline in hepatocytes infected with HBV (169).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

et al. 2022

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As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.

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Section: Discussionmentioning

confidence: 99%

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

et al. 2022

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“…At ~16 h after infection, the cells were washed three times with phosphate-buffered saline (PBS), and then maintained in medium supplemented with 2.5% dimethyl sulfoxide. To infect PHHs, cells were incubated with HBV at 10 2 vge/cell as described previously ( 8 , 48 , 49 ).…”

Section: Methodsmentioning

confidence: 99%

“…As described as previously ( 8 , 19 , 48 , 49 ), cells or liver tissues were lysed at 4°C in lysis buffer (25 mM Tris-HCl [pH 7.6], 150 mM NaCl, 1% NP-40, and 0.1% sodium dodecyl sulfate [SDS] plus protease inhibitor cocktail and phenylmethylsulfonyl fluoride). Extracted proteins were separated by SDS-PAGE and transferred onto polyvinylidene fluoride membranes.…”

Section: Methodsmentioning

confidence: 99%

“…As described previously ( 8 , 19 , 48 , 49 ), total RNA from cells or liver tissues was extracted using TRIzol (TaKaRa, Dalian, China) according to the manufacturer’s protocol and reverse transcribed into cDNA, followed by quantitative real-time PCR using a Roche LightCycler 480 II and Hieff qPCR SYBR Green Master Mix (Yeasen Biotechnology, Shanghai, China). The primers used in this study are provided in Table S3.…”

Section: Methodsmentioning

confidence: 99%

“…Extraction and quantification of core particle-associated HBV DNA were performed as described previously ( 8 , 48 – 51 ). For Southern blot analysis, HBV DNA was separated on a 1% agarose gel, transferred onto a positively charged nylon membrane (Roche, Mannheim, Germany), and hybridized with a digoxigenin-labeled full-length HBV probe.…”

Section: Methodsmentioning

confidence: 99%

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Forkhead O Transcription Factor 4 Restricts HBV Covalently Closed Circular DNA Transcription and HBV Replication through Genetic Downregulation of Hepatocyte Nuclear Factor 4 Alpha and Epigenetic Suppression of Covalently Closed Circular DNA via Interacting with Promyelocytic Leukemia Protein

Gong

et al. 2022

J Virol

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RNA‐binding motif protein 24 inhibits HBV replication in vivo

Yao

Chen

Huang

et al. 2023

Journal of Medical Virology

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Despite the extensive use of effective vaccines and antiviral drugs, chronic hepatitis B virus (HBV) infection continues to pose a serious threat to global public health. Therapies with novel mechanisms of action against HBV are being explored for achieving a functional cure. In this study, five murine models of HBV replication were used to investigate the inhibitory effect of RNA binding motif protein 24 (RBM24) on HBV replication. The findings revealed that RBM24 serves as a host restriction factor and suppresses HBV replication in vivo. The transient overexpression of RBM24 in hydrodynamics‐based mouse models of HBV replication driven by the CMV or HBV promoters suppressed HBV replication. Additionally, the ectopic expression of RBM24 decreased viral accumulation and the levels of HBV covalently closed circular DNA (cccDNA) in an rcccDNA mouse model. The liver‐directed transduction of adeno‐associated viruses (AAV)‐RBM24 mediated the stable hepatic expression of RBM24 in pAAV‐HBV1.2 and HBV/tg mouse models, and markedly reduced the levels of HBV cccDNA and other viral indicators. Altogether, these findings revealed that RBM24 inhibits the replication of HBV in vivo, and RBM24 may be a potential therapeutic target for combating HBV infections.

show abstract

STING signaling activation inhibits HBV replication and attenuates the severity of liver injury and HBV-induced fibrosis

Cited by 40 publications

References 86 publications

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

Forkhead O Transcription Factor 4 Restricts HBV Covalently Closed Circular DNA Transcription and HBV Replication through Genetic Downregulation of Hepatocyte Nuclear Factor 4 Alpha and Epigenetic Suppression of Covalently Closed Circular DNA via Interacting with Promyelocytic Leukemia Protein

RNA‐binding motif protein 24 inhibits HBV replication in vivo

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