Hepatitis B virus-specific miRNAs and Argonaute2 play a role in the viral life cycle.

Abstract

UNLABELLED:

Disease-specific serum miRNA profiles may serve as biomarkers and might reveal potential new avenues for therapy. An HBV-specific serum miRNA profile associated with HBV surface antigen (HBsAg) particles has recently been reported, and AGO2 and miRNAs have been shown to be stably associated with HBsAg in serum. We identified HBV-associated serum miRNAs using the Toray 3D array system in 10 healthy controls and 10 patients with chronic hepatitis B virus (HBV) infection. 19 selected miRNAs were then measured by quantitative RT-PCR in 248 chronic HBV patients and 22 healthy controls. MiRNA expression in serum versus liver tissue was also compared using biopsy samples. To examine the role of AGO2 during the HBV life cycle, we analyzed intracellular co-localization of AGO2 and HBV core (HBcAg) and surface (HBsAg) antigens using immunocytochemistry and proximity ligation assays in stably transfected HepG2 cells. The effect of AGO2 ablation on viral replication was assessed using siRNA. Several miRNAs, including miR-122, miR-22, and miR-99a, were up-regulated at least 1.5 fold (P<2E-08) in serum of HBV-infected patients. AGO2 and HBcAg were found to physically interact and co-localize in the ER and other subcellular compartments. HBs was also found to co-localize with AGO2 and was detected in multiple subcellular compartments. Conversely, HBx localized non-specifically in the nucleus and cytoplasm, and no interaction between AGO2 and HBx was detected. SiRNA ablation of AGO2 suppressed production of HBV DNA and HBs antigen in the supernatant.

CONCLUSION:

These results suggest that AGO2 and HBV-specific miRNAs might play a role in the HBV life cycle.

• Authors: C Nelson Hayes, Sakura Akamatsu, Masataka Tsuge, Daiki Miki, Rie Akiyama, Hiromi Abe, Hidenori Ochi, Nobuhiko Hiraga, Michio Imamura, Shoichi Takahashi, Hiroshi Aikata, Tomokazu Kawaoka, Yoshiiku Kawakami, Waka Ohishi, Kazuaki Chayama
• Journal: PloS one (PLoS One) Vol. 7 Issue 10 Pg. e47490 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23091627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AGO2 protein, human
• Argonaute Proteins
• Hepatitis B Core Antigens
• Hepatitis B Surface Antigens
• MicroRNAs

Topics

• Adolescent
• Adult
• Aged
• Argonaute Proteins (genetics, metabolism)
• Case-Control Studies
• Cell Line
• Female
• Gene Expression Profiling
• Hepatitis B (genetics, metabolism)
• Hepatitis B Core Antigens (metabolism)
• Hepatitis B Surface Antigens (blood, metabolism)
• Hepatitis B virus (physiology)
• Humans
• Male
• MicroRNAs (blood, genetics, metabolism)
• Middle Aged
• Molecular Sequence Data
• Protein Binding
• RNA Interference
• Signal Transduction
• Virus Replication
• Young Adult