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

Jiang, Junyi; Tang, Hong

doi:10.1007/s13238-010-0141-8

Cited by 82 publications

(74 citation statements)

References 53 publications

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“…Because RLRs are cytosolic viral sensors and HBV nucleic acids may be present in the cytosol in addition to the nucleus as described in the aforementioned paragraph, HBV is more likely to be recognized by RLRs. Consistent with this notion, recent studies have demonstrated that overexpression of IPS-1 in a hepatoma cell line transfected with the HBV replicative plasmid significantly suppresses HBV replication (15), and that HBV X protein interacts with IPS-1 and disrupts the downstream signaling of RLRs to prevent the production of type I IFNs induced by Sendai virus, vesicular stomatitis virus (VSV), or poly (dA:dT) (16)(17)(18)(19). Furthermore, two studies have shown that HBV pol impairs the activation of TBK1/IKKε, the downstream signaling molecule of IPS-1 in the RLR signaling pathway (20,21).…”

Section: H Uman Hepatitis B Virus (Hbv) Is a Small (32-kb)mentioning

confidence: 75%

“…Altogether, these studies suggest that IPS-1 is likely involved in the innate response against HBV infection. Given that RIG-I and MDA5 are upstream molecules of IPS-1 (22) and that IPS-1 is involved in the innate response against HBV (15)(16)(17)(18)(19)(20)(21), RIG-I and MDA5 may play a role in the regulation of HBV infection.…”

Section: H Uman Hepatitis B Virus (Hbv) Is a Small (32-kb)mentioning

confidence: 99%

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Melanoma Differentiation–Associated Gene 5 Senses Hepatitis B Virus and Activates Innate Immune Signaling To Suppress Virus Replication

Lu¹,

Liao

2013

The Journal of Immunology

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Retinoic acid–inducible gene-I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5) belong to the RIG-I–like receptors family of pattern recognition receptors. Both RIG-I and MDA5 have been shown to recognize various viral RNAs, but whether they mediate hepatitis B virus (HBV) infection remains unclear. In this study, we demonstrated that the expression of MDA5, but not RIG-I, was increased in Huh7 cells transfected with the HBV replicative plasmid and in the livers of mice hydrodynamically injected with the HBV replicative plasmid. To further determine the effect of RIG-I–like receptors on HBV replication, we cotransfected the HBV replicative plasmid with RIG-I or MDA5 expression plasmid into Huh7 cells and found that MDA5, but not RIG-I at a similar protein level, significantly inhibited HBV replication. Knockdown of endogenous MDA5, but not RIG-I, in Huh7 cells transfected with the HBV replicative plasmid significantly increased HBV replication. Of particular interest, we found that MDA5, but not RIG-I, was able to associate with HBV-specific nucleic acids, suggesting that MDA5 may sense HBV. Finally, we performed in vivo experiments by hydrodynamic injection of the HBV replicative plasmid into wild-type, MDA5−/−, MDA5+/−, or RIG-I+/− mice, and found that MDA5−/− and MDA5+/− mice, but not RIG-I+/− mice, exhibited an increase of HBV replication as compared with wild-type mice. Collectively, our in vitro and in vivo studies both support a critical role for MDA5 in the innate immune response against HBV infection.

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Section: H Uman Hepatitis B Virus (Hbv) Is a Small (32-kb)mentioning

confidence: 75%

Section: H Uman Hepatitis B Virus (Hbv) Is a Small (32-kb)mentioning

confidence: 99%

Melanoma Differentiation–Associated Gene 5 Senses Hepatitis B Virus and Activates Innate Immune Signaling To Suppress Virus Replication

Lu¹,

Liao

2013

The Journal of Immunology

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“…A number of viruses encode deubiquitination enzymes (DUBs) to manipulate cellular processes, and several virally encoded DUBs have been shown to antagonize IFN signaling (13,28,30,34). Recently, a number of studies have shown that herpesviridae have large tegument proteins with a DUB domain embedded at their N terminus, such as herpes simplex virus 1 (HSV-1) UL36 USP , mouse cytomegalovirus (MCMV) M48, human cytomegalovirus (HCMV) UL48, EBV BPLF1, and KSHV and MHV68 ORF64 (11,14,25,26,31).…”

mentioning

confidence: 99%

Inhibition of RIG-I-Mediated Signaling by Kaposi's Sarcoma-Associated Herpesvirus-Encoded Deubiquitinase ORF64

Inn

Lee

Rathbun

et al. 2011

J Virol

141

150

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“…On the other hand, chronic HBV infection as the main reason of liver transplant in Iran (42,43) causes tissue inflammation and dysfunction (8) It is documented that HBV proteins such as HBV polymerase, HBx, and HBsAg interfered in IRF3 and IRF7 functions to deal with innate immune responses (28,(31)(32)(33). Despite the fact, the innate immune system reduces HBV replication and HBV-mRNA stability (44,45).…”

Section: Discussionmentioning

confidence: 99%

“…HBV polymerase blocked phosphorylation, dimerization, and activation of IRF3 and consequently reduced the production and antiviral effect of IFN-β (31,32). HBx as a deubiquitinating enzyme also promoted proteasome degradation of RIG-1, TRAF3, and IRF3 factors (33). Modification in IRF3 and IRF7 mRNA is not yet investigated in human or animal models of transplantation.…”

Section: Introductionmentioning

confidence: 99%

Study the Cross-talk Between Hepatitis B Virus Infection and Interferon Regulatory Factors in Liver Transplant Patients

et al. 2017

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Background: Interferon regulatory factors (IRFs) as immunoregulatory molecules have a determinative antiviral role in liver transplantation outcomes and graft rejection. Hepatitis B virus (HBV) and its antigen derivatives also choose some strategies to escape from innate immune responses. Objectives: The current study aimed at evaluating inflammatory cross-talks between pattern recognition receptors (PRRs) signaling components such as IRF3 and IRF7 with HBV infection in mRNA levels in patients undergoing liver transplantation. Methods: The 46 HBV infected liver recipients were divided into rejection experienced (20) and not experienced (26) groups and a healthy control group was also considered. Peripheral mononuclear cells (PBMCs) were isolated form each studied patient on the days 1, 4, and 7 in post-transplant period. After RNA extraction and cDNA synthesis from each collected sample, the expression levels of IRF3 and IRF7 genes were evaluated using in-house SYBER Green based the real-time polymerase chain reaction (PCR) protocols. Results: The overexpression of mRNA levels of IRF3 (3.37 folds) and IRF7 (1.74 folds) on the day 1 were found in patients experiencing rejection, compared with non-rejected ones, based on initial ischemia/reperfusion (I/R) injuries. But, the mRNA levels of IRF3 (0.53 folds) and IRF7 (0.74 folds) on the day 4 were downregulated in patients with rejected transplantation, compared with non-rejected ones. Finally, reducing the expression of IRF3 (0.54 fold) on the day 7 and upregulation of IRF7 (2.38 fold) on the day 7 were found in rejected liver recipients, compared with non-rejected ones in post-transplant period. Conclusions: Downregulation of IRF3 expression in patients with HBV infection, who experienced rejection episodes in the first week post-liver transplantation indicated that they may be at higher risk for acute rejection; the hypothesis, which should be investigated in further studies.

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

Cited by 82 publications

References 53 publications

Melanoma Differentiation–Associated Gene 5 Senses Hepatitis B Virus and Activates Innate Immune Signaling To Suppress Virus Replication

Melanoma Differentiation–Associated Gene 5 Senses Hepatitis B Virus and Activates Innate Immune Signaling To Suppress Virus Replication

Inhibition of RIG-I-Mediated Signaling by Kaposi's Sarcoma-Associated Herpesvirus-Encoded Deubiquitinase ORF64

Study the Cross-talk Between Hepatitis B Virus Infection and Interferon Regulatory Factors in Liver Transplant Patients

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