MicroRNAs-372/373 promote the expression of hepatitis B virus through the targeting of nuclear factor I/B

Guo, Hongyan; Liu, Haiying; Mitchelson, Keith; Rao, Huiying; Luo, Mingyong; Xie, Liang; Sun, Yimin; Zhang, Liang; Lü, Ying; Liu, Ruyu; Ren, Aihui; Liu, Shuai; Zhou, Shuai; Zhu, Jinmin; Zhou, Yuxiang; Huang, Ailong; Wei, Lai; Guo, Yiming; Cheng, Jing

doi:10.1002/hep.24441

Cited by 116 publications

(83 citation statements)

References 36 publications

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“…Interestingly, miR-373 upregulation does not correlate with HCV load in patient sera. miR-373 was upregulated in HBV-infected liver tissues, and miR-373 expression promotes HBV expression by involving the NFIB transcription factor (32), although modulation of the JAK/STAT signaling pathway was not studied. Since miR-373 expression is upregulated in chronic HCV infection and modulates the innate immune system, it will be important to investigate the status of miR-373 in other chronic infections.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus-Mediated Enhancement of MicroRNA miR-373 Impairs the JAK/STAT Signaling Pathway

Mukherjee

Bisceglie

2015

J Virol

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Hepatitis C virus (HCV) is a serious global health problem and establishes chronic infection in a significant number of infected humans worldwide. Interferon (IFN) and IFN-stimulated genes (ISGs) are amplified during HCV infection but fail to eliminate virus from the liver in a large number of infected patients, and the mechanism is not fully understood. MicroRNAs (miRNAs) have been implicated in the control of many biological processes, including IFN signaling. To gain more insights into the role of cellular miRNAs in possible countermeasures of HCV for suppression of the host antiviral response, a miRNA array was performed by using primary human hepatocytes infected with in vitro cell culture-grown HCV. A group of miRNAs were modulated in HCV-infected primary human hepatocytes. We focused on miR-373, as this miRNA was significantly upregulated in HCV-infected primary human hepatocytes. Here, we analyzed the function of miR-373 in the context of HCV infection. HCV infection upregulates miR-373 expression in hepatocytes and HCV-infected liver biopsy specimens. Furthermore, we discovered that miR-373 directly targets Janus kinase 1 (JAK1) and IFN-regulating factor 9 (IRF9), important factors in the IFN signaling pathway. The upregulation of miR-373 by HCV also inhibited STAT1 phosphorylation, which is involved in ISG factor 3 (ISGF3) complex formation and ISG expression. The knockdown of miR-373 in hepatocytes enhanced JAK1 and IRF9 expression and reduced HCV RNA replication. Taken together, our results demonstrated that miR-373 is upregulated during HCV infection and negatively regulated the type I IFN signaling pathway by suppressing JAK1 and IRF9. Our results offer a potential therapeutic approach for antiviral intervention. H epatitis C virus is a member of the Hepacivirus genus of theFlaviviridae family and is represented by seven major genotypes. The virion contains a 9.6-kb single-stranded RNA genome of positive polarity, with highly invariant 5= and 3= untranslated regions (UTRs) flanking a long open reading frame (ORF) that is translated via an internal ribosome entry site (IRES) (1). The resulting polyprotein is processed by viral and cellular proteases to yield structural (core, E1, and E2/p7) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins.HCV infection is one of the main causes of chronic liver disease. It is estimated that ϳ200 million people are chronically infected with HCV worldwide (2, 3). Chronic HCV infection is linked to a deregulation of innate and adaptive immune signaling mechanisms (4). Despite progress in understanding immunity against HCV infection and its pathogenesis along with the development of highly effective direct-acting antivirals (DAAs), a prophylactic anti-HCV vaccine is still lacking, and at least 2 million new HCV infections occur each year (5).MicroRNAs (miRNAs) are a class of ϳ18-to 22-nucleotidelong noncoding RNA molecules that function through posttranscriptional regulation of gene expression. The production of miRNAs requires several processi...

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Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus-Mediated Enhancement of MicroRNA miR-373 Impairs the JAK/STAT Signaling Pathway

Mukherjee

Bisceglie

2015

J Virol

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“…Despite inhibition of HBV infection by miRNA machinery, some miRNAs appear to have positive effects on HBV replication. The miR-372/373 promotes HBV expression by targeting the nuclear factor I/B (16), and miR-1 enhances HBV replication by targeting the host gene histone deacetylase 4 (17). Considerable progress has been made in the understanding of miRNAs and HBV replication, but the complex regulatory networks involving miRNAs have not been evaluated comprehensively in HBV replication.…”

Section: Hepatitis B Virus (Hbv)mentioning

confidence: 99%

MicroRNA-26b Inhibits Hepatitis B Virus Transcription and Replication by Targeting the Host Factor CHORDC1 Protein

Zhao¹,

Xu²,

Zhou³

et al. 2014

Journal of Biological Chemistry

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Background: Disordered miR-26b expression has been linked to the development of many diseases induced by hepatitis B virus (HBV). Results: miR-26b inhibits HBV replication, and HBV infection suppresses miR-26b expression. Conclusion: miR-26b acts as a host restriction factor to attenuate HBV transcription and replication. Significance: The functional interplay between HBV infection and miR-26b may influence the outcome of viral proliferation and virus-induced diseases.

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“…*, P Ͻ 0.05; **, P Ͻ 0.01; ***, P Ͻ 0.001. and PRRSV titers (data not shown), which indicated that NFIA, NFIB, IRAK1, IRAK4, IRF1, IRF9, IFNAR1, and IFNAR2 are involved in PRRSV replication regulated by miR-373. Previous studies have shown that NFIB (35) and IRF9 (36) were the target genes of miR-373, so NFIA, NFIB, IRAK1, IRAK4, IRF1, and IRF9 were selected to confirm that the potential target genes described above were also the target genes of miR-373.…”

mentioning

confidence: 99%

MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction

Chen

Shi

Zhang

et al. 2017

J Virol

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MicroRNAs (miRNAs) play an important role in the regulation of immune responses. Previous studies have indicated that dysregulating the miRNAs leads to the immunosuppression of porcine reproductive and respiratory syndrome virus (PRRSV). However, it is not clear how PRRSV regulates the expression of host miRNA, which may lead to immune escape or promote the replication of the virus. The present work suggests that PRRSV upregulated the expression of miR-373 through elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells. Furthermore, this work demonstrated that miR-373 promoted the replication of PRRSV, since miR-373 was a novel negative miRNA for the production of beta interferon (IFN-␤) by targeting nuclear factor IA (NFIA), NFIB, interleukin-1 receptor-associated kinase 1 (IRAK1), IRAK4, and interferon regulatory factor 1 (IRF1). We also found that both NFIA and NFIB were novel proteins for inducing the production of IFN-␤, and both of them could inhibit the replication of PRRSV. In conclusion, PRRSV upregulated the expression of miR-373 by elevating the expression of Sp1 and hijacked the host miR-373 to promote the replication of PRRSV by negatively regulating the production of IFN-␤.IMPORTANCE PRRSV causes one of the most economically devastating diseases of swine, and there is no effective method for controlling PRRSV. It is not clear how PRRSV inhibits the host's immune response and induces persistent infection. Previous studies have shown that PRRSV inhibited the production of type I IFN, and the treatment of type I IFN could efficiently inhibit the replication of PRRSV, so it will be helpful to design new methods of controlling PRRSV by understanding the molecular mechanism by which PRRSV modulated the production of IFN. The current work shows that miR-373, upregulated by PRRSV, promotes PRRSV replication, since miR-373 impaired the production of IFN-␤ by targeting NFIA, NFIB, IRAK1, IRAK4, and IRF1, and both NFIA and NFIB were antiviral proteins to PRRSV. In conclusion, this paper revealed a novel mechanism of PRRSV that impaired the production of type I IFN by upregulating miR-373 expression in MARC-145 cells.

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MicroRNAs-372/373 promote the expression of hepatitis B virus through the targeting of nuclear factor I/B

Cited by 116 publications

References 36 publications

Hepatitis C Virus-Mediated Enhancement of MicroRNA miR-373 Impairs the JAK/STAT Signaling Pathway

Hepatitis C Virus-Mediated Enhancement of MicroRNA miR-373 Impairs the JAK/STAT Signaling Pathway

MicroRNA-26b Inhibits Hepatitis B Virus Transcription and Replication by Targeting the Host Factor CHORDC1 Protein

MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction

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