Hepatitis C Virus Infection and Hepatic Stellate Cell Activation Downregulate miR-29: miR-29 Overexpression Reduces Hepatitis C Viral Abundance in Culture

Bandyopadhyay, Sarmistha; Friedman, Robin; Marquez, Rebecca T.; Keck, Kathy; Kong, Benjamin Y.; Icardi, Michael; Brown, Kyle E.; Burge, Christopher B.; Schmidt, Warren N.; Wang, Yulei; McCaffrey, Anton P.

doi:10.1093/infdis/jir186

Cited by 141 publications

(122 citation statements)

References 46 publications

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“…A number of cellular miRNAs have been found to regulate HCV infection (9,25,31,32). In response to IFN treatment, host cells initiate an antiviral defense mechanism that involves the induction of certain miRNAs that suppress viral mRNA replication and the inhibition of other cellular miRNAs that promote the viral life cycle.…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Profiling of Alpha Interferon- and Interleukin-28B-Regulated MicroRNAs and Identification of let-7s with Anti-Hepatitis C Virus Activity by Targeting IGF2BP1

Cheng

Niu

et al. 2013

J Virol

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Hepatitis C virus (HCV) infection is a major cause of severe liver disease. Interferon (IFN)/ribavirin treatment remains the standard therapeutic regimen for HCV infection in most countries. IFN-stimulated genes are believed to contribute to antiviral effects. However, emerging evidence suggests that microRNAs (miRNAs), a class of noncoding small RNAs, are involved in the control of viral infection. Here, we systematically profiled the hepatocyte expression of a set of 750 miRNAs in response to alpha interferon (IFN-␣) and interleukin-28B (IL-28B) treatments. The anti-HCV activity of differentially expressed miRNAs was evaluated using cell culture-derived HCV in vitro. The results demonstrate that let-7b had a significant anti-HCV effect by inhibiting HCV replication and viral protein translation in human hepatoma cells. In particular, we show that the inhibition of let-7b attenuated the anti-HCV effects of IFN-␣ and IL-28B. Furthermore, we show that the host factor insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is a target of let-7b. IGF2BP1 was required for HCV replication, and its expression was downregulated by IFN-␣ and IL-28B. Deletion of the wild-type seed region of let-7b abolished its antiviral activity. Finally, we demonstrate that other let-7 family miRNAs were able to inhibit HCV and to suppress IGF2BP1 expression. In conclusion, we provide an example of a host miRNA regulated by type I and type III IFNs that inhibits HCV replication and infectivity by targeting host targets. These results highlight the important role of miRNAs in the host antiviral immune response and provide a novel candidate for anti-HCV therapy.

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Section: Discussionmentioning

confidence: 99%

High-Throughput Profiling of Alpha Interferon- and Interleukin-28B-Regulated MicroRNAs and Identification of let-7s with Anti-Hepatitis C Virus Activity by Targeting IGF2BP1

Cheng

Niu

et al. 2013

J Virol

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“…Although IGF-I has also been shown to induce apoptosis in HSC, 50 in cooperation with PDGF-BB, it certainly functions as an important mitogen for hepatic myofibroblasts. 51,52 Accordingly, miR-29, shown to affect moderately HSC proliferation, 53 might be involved in HSC growth by posttranscriptional IGF-I synthesis control.…”

Section: Discussionmentioning

confidence: 99%

Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29

Kwiecinski

Elfimova

Noetel

et al. 2012

Laboratory Investigation

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“…[11][12][13] Serum miR-29a is significantly lower in patients with advanced liver cirrhosis than in healthy controls or patients with early fibrosis. 12 Further it has been shown that overexpression of miR-29 in murine HSC resulted in the downregulation of collagen expression 12,14 through a mechanism that directly targets the mRNA expression of ECM genes. These findings suggest that miR-29 may be an important therapeutic target in chronic liver disease.…”

Section: Introductionmentioning

confidence: 99%

MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice

et al. 2016

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Hepatitis C Virus Infection and Hepatic Stellate Cell Activation Downregulate miR-29: miR-29 Overexpression Reduces Hepatitis C Viral Abundance in Culture

Abstract: HCV infection downregulates miR-29 in hepatocytes and may potentiate collagen synthesis by reducing miR-29 levels in activated HSCs. Treatment with miR-29 mimics in vivo might inhibit HCV while reducing fibrosis.

Cited by 141 publications

References 46 publications

High-Throughput Profiling of Alpha Interferon- and Interleukin-28B-Regulated MicroRNAs and Identification of let-7s with Anti-Hepatitis C Virus Activity by Targeting IGF2BP1

High-Throughput Profiling of Alpha Interferon- and Interleukin-28B-Regulated MicroRNAs and Identification of let-7s with Anti-Hepatitis C Virus Activity by Targeting IGF2BP1

Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29

MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice

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