The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein

Wei, Congwen; Ni, Caifei; Song, Ting; Liu, Yu; Yang, Xiaoli; Zheng, Zhu-Jun; Jia, Yongxia; Yuan, Yuan; Guan, Kai; Xu, Yang; Cheng, Xiaozhong; Zhang, Yanhong; Yang, Xiao; Wang, Youliang; Wen, Chaoyang; Wu, Qing; Shi, Wei; Zhong, Hui

doi:10.4049/jimmunol.0903874

Cited by 203 publications

(190 citation statements)

References 48 publications

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…In line with this notion, Pin1, which negatively regulates IRF3 signaling (Saitoh et al, 2006), is overexpressed prevalently in HBV-HCC positive for HBx (Pang et al, 2007). In addition, reduced CARDIF protein levels have been recently reported to correlate well with HBx expression in HBV-HCC (Wei et al, 2010). This downregulation is ascribed to the degradation of CARDIF promoted by HBx, providing another way by which HBx can interfere with RIG I/ MDA5 signaling (Wei et al, 2010).…”

Section: Discussionmentioning

confidence: 76%

“…In addition, reduced CARDIF protein levels have been recently reported to correlate well with HBx expression in HBV-HCC (Wei et al, 2010). This downregulation is ascribed to the degradation of CARDIF promoted by HBx, providing another way by which HBx can interfere with RIG I/ MDA5 signaling (Wei et al, 2010). Nevertheless, it is somewhat controversial whether HBx influences production of type I IFN in the context of viral replication in HepG2 cells (Wang and Ryu, 2010;Wei et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Jiang

Tang

2010

Protein Cell

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Jiang

Tang

2010

Protein Cell

View full text Add to dashboard Cite

show abstract

“…In mice, hepatitis B surface antigens (HBsAg), hepatitis envelope antigen (HBeAg), and HBV virions are capable of inhibiting TLR-dependent pathways [25]. HBV-X protein directly degrades adaptor molecule MAVS, resulting in the inhibition of RIG-I-dependent signaling pathways [26]. In the shared downstream pathway of TLR and RIG-I, HBV polymerase is responsible for IRF3 inhibition at the levels of kinases TBK1/IKKe [27] and has been reported to inhibit STING-stimulated IRF3 activation and IFN-b induction [28].…”

Section: Pattern Recognition Receptors In Hbv Infectionmentioning

confidence: 99%

Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

show abstract

“…36 HBx protein was reported to inhibit RIG-I-mediated IFN-b induction by promoting ubiquitin-dependent degradation of IPS-1 in hepatoma cells. [37][38][39] HBV polymerase was shown to suppress RIG-I-induced IFN-b induction by interference with IRF3 phosphorylation and nuclear translocation and inhibiting the interaction between TBK1/IKKe and DDX3 in human hepatocytes. 34,40 The mechanisms employed by HBV to counteract innate immune system are summarized in Table 1.…”

Section: Interaction Between Tlrs and Hbvmentioning

confidence: 99%

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

Zhang

Yang

et al. 2014

Cell Mol Immunol

View full text Add to dashboard Cite

It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus (HBV) infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors (TLRs) sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons (IFNs) and pro-inflammatory cytokines. Experimental results from in vitro and in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T-and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

show abstract

The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein

Abstract: Material Supplementary 4.DC1http://www.jimmunol.org/content/suppl/2010/06/16/jimmunol.090387

Cited by 203 publications

References 48 publications

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Host–virus interactions in hepatitis B and hepatitis C infection

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

Contact Info

Product

Resources

About