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Functional interplay between hepatitis B virus X protein and human miR-125a in HBV infection.

Abstract
The hepatitis B virus (HBV) is a widespread human pathogen and chronic HBV infection is a major risk factor for hepatocellular carcinoma (HCC). Some cellular microRNAs are emerging as important regulators of virus-host interaction, indirectly or directly modulating HBV replication and pathogenesis. miR-125a binds the viral transcript encoding the surface antigen and interferes with its expression, thus inhibiting viral replication. Intriguingly, liver miR-125a expression has been found increased in patients with high levels of hepatic HBV-DNA. The present study investigates the mechanism by which liver exposure to HBV induces the expression of miR-125a. The analyses were first performed on liver biopsies from HBV patients, showing that the expression of the viral transactivator X protein (HBx) paralleled the increase of miR-125a expression. Then, transfection of HCC cell lines with an HBx-expressing vector showed a substantial increase of miR-125a expression. Overall, the available data depict a self-inhibitory feedback loop in which HBV, through HBx, increases the expression of miR-125a, that in turn interferes with expression of HBV surface antigen, thus repressing viral replication.
AuthorsNicola Mosca, Filomena Castiello, Nicola Coppola, Maria Consiglia Trotta, Caterina Sagnelli, Mariantonietta Pisaturo, Evangelista Sagnelli, Aniello Russo, Nicoletta Potenza
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 449 Issue 1 Pg. 141-5 (Jun 20 2014) ISSN: 1090-2104 [Electronic] United States
PMID24824183 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • MIRN125 microRNA, human
  • MicroRNAs
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
Topics
  • Adult
  • Female
  • Hepatitis B (immunology)
  • Hepatitis B virus (immunology)
  • Humans
  • Liver (immunology, virology)
  • Male
  • MicroRNAs (immunology)
  • Middle Aged
  • Protein Binding
  • Tissue Distribution
  • Trans-Activators (immunology)
  • Viral Load (immunology)
  • Viral Regulatory and Accessory Proteins

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