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

Zhao, Fanpeng; Xu, Gang; Zhou, Yaqin; Wang, Lvyin; Xie, Jiajia; Ren, Shifang; Shi, Lei; Zhu, Ying

doi:10.1074/jbc.m114.589978

Cited by 43 publications

(35 citation statements)

References 46 publications

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“…miRNAs are involved in the regulation of diverse processes, including apoptosis, metabolism, cell fate determination, and host-pathogen interactions (9). miRNAs have been shown to regulate the host antiviral response by altering the expression of host genes required for virus replication and antiviral response (10)(11)(12) or by directly targeting viral genomes and/or transcripts (13)(14)(15)(16)(17).…”

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confidence: 99%

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

Slonchak

Shannon

Pali

et al. 2016

J Virol

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West Nile virus (WNV) is a mosquito-transmitted flavivirus that naturally circulates between mosquitos and birds but can also infect humans, causing severe neurological disease. The early host response to WNV infection in vertebrates primarily relies on the type I interferon pathway; however, recent studies suggest that microRNAs (miRNAs) may also play a notable role. In this study, we assessed the role of host miRNAs in response to WNV infection in human cells. We employed small RNA sequencing (RNA-seq) analysis to determine changes in the expression of host miRNAs in HEK293 cells infected with an Australian strain of WNV, Kunjin (WNV KUN ), and identified a number of host miRNAs differentially expressed in response to infection. Three of these miRNAs were confirmed to be significantly upregulated in infected cells by quantitative reverse transcription (qRT)-PCR and Northern blot analyses, and one of them, miR-532-5p, exhibited a significant antiviral effect against WNV KUN infection. We have demonstrated that miR-532-5p targets and downregulates expression of the host genes SESTD1 and TAB3 in human cells. Small interfering RNA (siRNA) depletion studies showed that both SESTD1 and TAB3 were required for efficient WNV KUN replication. We also demonstrated upregulation of mir-532-5p expression and a corresponding decrease in the expression of its targets, SESTD1 and TAB3, in the brains of WNV KUN -infected mice. Our results show that upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent a host antiviral response aimed at limiting WNV KUN infection and highlight the important role of miRNAs in controlling RNA virus infections in mammalian hosts. IMPORTANCEWest Nile virus (WNV) is a significant viral pathogen that poses a considerable threat to human health across the globe. There is no specific treatment or licensed vaccine available for WNV, and deeper insight into how the virus interacts with the host is required to facilitate their development. In this study, we addressed the role of host microRNAs (miRNAs) in antiviral response to WNV in human cells. We identified miR-532-5p as a novel antiviral miRNA and showed that it is upregulated in response to WNV infection and suppresses the expression of the host genes TAB3 and SESTD1 required for WNV replication. Our results show that upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent an antiviral response aimed at limiting WNV infection and highlight the important role of miRNAs in controlling virus infections in mammalian hosts. W est Nile virus (WNV) is a mosquito-transmitted flavivirus associated with outbreaks of encephalitis in humans and horses around the world (1). The most significant WNV outbreaks have occurred in North America, where a highly pathogenic strain of WNV emerged in New York in 1999. This strain rapidly spread to all the states and by 2011 had infected an estimated 1.8 million people, causing close to 360,000 illnesses and ϳ1,300 deaths (2). The majority of ...

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confidence: 99%

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

Slonchak

Shannon

Pali

et al. 2016

J Virol

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“…As reported previously, hepatitis B virus (HBV) infection is considered as a major threat for HCC, and most patients suffered from HCC as a consequence of persistent HBV infection, especially in China . Moreover, over 350 million people was estimated to be chronically infected with HBV, included 50% of male and 14% of female carriers, who would eventually die of liver cirrhosis and HCC . Thus, it is of great values to elucidate the pathogenesis of HBV infection‐induced HCC.…”

Section: Introductionmentioning

confidence: 99%

Influence of miR‐520e‐mediated MAPK signalling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2

Tian

Zhang

et al. 2019

Journal of Viral Hepatitis

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Summary We determined the role of miR‐520e in the replication of hepatitis B virus (HBV) and the growth of hepatocellular carcinoma (HCC) cells. MiR‐520e and EPH receptor A2 (EphA2) in HBV‐positive HCC tissues and cells were detected, and we studied the impact of miR‐520e and the EphA2 receptor in cellular and murine HBV replication models. We find that MiR‐520e was upregulated and EphA2 was downregulated in HBV‐positive HCC tissues and cells. MiR‐520e was decreased in Huh7‐X and HepG2‐X cells in which HBx was stably expressed, but was dose‐dependently elevated after interfering with HBx. Additionally, miR‐520e mimic and si‐EphA2 groups were reduced in association with increases in HBV DNA content, HBsAg and HBeAg levels, cell proliferation and were enhanced in the expressions of EphA2, p‐p38MAPK/p38MAPK, phosphorylated extracellular signal‐regulated kinase 1/2 (p‐ERK1/2)/ERK1/2 and cell apoptosis. Furthermore, si‐EphA2 reversed the promotion effect of miR‐520e inhibitor on HBV replication and tumour cell growth. Upregulating miR‐520e in rAAV8‐1.3HBV‐infected mouse resulted in reduced EphA2 in liver tissues and HBV DNA content in serum. We find that MiR‐520e was decreased in HBV‐positive HCC, while overexpression of miR‐520e blocked p38MAPK and ERK1/2 signalling pathways by an inhibitory effect on EphA2 and ultimately reduced HBV replication and inhibited tumour cell growth. These data indicate a role for miR‐520e in the regulation of HBV replication.

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“…HBV expresses seven proteins, 30,31 and the x protein interferes with cellular processes and host transcription. 32,33 Interestingly, only HBV x protein could induce Rubicon expression (Figure 2g) after pRubicon-luc and each HBV gene had been co-transfected in Huh7 cells.…”

Section: Hbv Enhances Rubicon Expression In Hepatocytesmentioning

confidence: 99%

Inducible Rubicon facilitates viral replication by antagonizing interferon production

et al. 2017

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The RUN domain Beclin-1-interacting cysteine-rich-containing (Rubicon) protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner, but little is known regarding the role of Rubicon during viral infection. Here, we performed functional studies of the identified target in interferon (IFN) signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN. The Rubicon protein levels were elevated in peripheral blood mononuclear cells, sera and liver tissues from patients with hepatitis B virus (HBV) infection relative to those in healthy individuals. Assays of the overexpression and knockdown of Rubicon showed that Rubicon significantly promoted HBV replication. In addition, Rubicon knockdown resulted in the inhibition of enterovirus 71, influenza A virus and vesicular stomatitis virus. The expression o0f Rubicon led to the suppression of virus-induced type-I interferon (IFN-α and IFN-β) and type-III interferon (IFN-λ1). Translocation of activated IRF3 and IRF7 from the cytoplasm to the nucleus was involved in this process, and the NF-κB essential modulator (NEMO), a key factor in the IFN pathway, was the target with which Rubicon interacted. Our results reveal a previously unrecognized function of Rubicon as a virus-induced protein that binds to NEMO, leading to the inhibition of type-I interferon production. Rubicon thus functions as an important negative regulator of the innate immune response, enhances viral replication and may play a role in viral immune evasion.

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

Cited by 43 publications

References 46 publications

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

Influence of miR‐520e‐mediated MAPK signalling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2

Inducible Rubicon facilitates viral replication by antagonizing interferon production

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