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Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling.

Publication ,  Journal Article
Jarret, A; McFarland, AP; Horner, SM; Kell, A; Schwerk, J; Hong, M; Badil, S; Joslyn, RC; Baker, DP; Carrington, M; Hagedorn, CH; Gale, M; Savan, R
Published in: Nat Med
December 2016

Hepatitis C virus (HCV) infects 200 million people globally, and 60-80% of cases persist as a chronic infection that will progress to cirrhosis and liver cancer in 2-10% of patients. We recently demonstrated that HCV induces aberrant expression of two host microRNAs (miRNAs), miR-208b and miR-499a-5p, encoded by myosin genes in infected hepatocytes. These miRNAs, along with AU-rich-element-mediated decay, suppress IFNL2 and IFNL3, members of the type III interferon (IFN) gene family, to support viral persistence. In this study, we show that miR-208b and miR-499a-5p also dampen type I IFN signaling in HCV-infected hepatocytes by directly down-regulating expression of the type I IFN receptor chain, IFNAR1. Inhibition of these miRNAs by using miRNA inhibitors during HCV infection increased expression of IFNAR1. Additionally, inhibition rescued the antiviral response to exogenous type I IFN, as measured by a marked increase in IFN-stimulated genes and a decrease in HCV load. Treatment of HCV-infected hepatocytes with type I IFN increased expression of myosins over HCV infection alone. Since these miRNAs can suppress type III IFN family members, these data collectively define a novel cross-regulation between type I and III IFNs during HCV infection.

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Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

December 2016

Volume

22

Issue

12

Start / End Page

1475 / 1481

Location

United States

Related Subject Headings

  • Receptor, Interferon alpha-beta
  • Myosins
  • MicroRNAs
  • Interleukins
  • Interferons
  • Interferon Type I
  • Immunology
  • Humans
  • Hepatocytes
  • Hepatitis C, Chronic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jarret, A., McFarland, A. P., Horner, S. M., Kell, A., Schwerk, J., Hong, M., … Savan, R. (2016). Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling. Nat Med, 22(12), 1475–1481. https://doi.org/10.1038/nm.4211
Jarret, Abigail, Adelle P. McFarland, Stacy M. Horner, Alison Kell, Johannes Schwerk, MeeAe Hong, Samantha Badil, et al. “Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling.Nat Med 22, no. 12 (December 2016): 1475–81. https://doi.org/10.1038/nm.4211.
Jarret A, McFarland AP, Horner SM, Kell A, Schwerk J, Hong M, et al. Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling. Nat Med. 2016 Dec;22(12):1475–81.
Jarret, Abigail, et al. “Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling.Nat Med, vol. 22, no. 12, Dec. 2016, pp. 1475–81. Pubmed, doi:10.1038/nm.4211.
Jarret A, McFarland AP, Horner SM, Kell A, Schwerk J, Hong M, Badil S, Joslyn RC, Baker DP, Carrington M, Hagedorn CH, Gale M, Savan R. Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling. Nat Med. 2016 Dec;22(12):1475–1481.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

December 2016

Volume

22

Issue

12

Start / End Page

1475 / 1481

Location

United States

Related Subject Headings

  • Receptor, Interferon alpha-beta
  • Myosins
  • MicroRNAs
  • Interleukins
  • Interferons
  • Interferon Type I
  • Immunology
  • Humans
  • Hepatocytes
  • Hepatitis C, Chronic