Question

“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.”

https://www.ncbi.nlm.nih.gov/pubmed/23091627

1. Which miRNAs were up-regulated in the serum of HBV infected individuals, compared to healthy individuals?

Answer 1

Several miRNas including miR-122, miR-22, miR-99A were up-regulated atleast 1.5 fold(P less than 2E-08) in serum of HBV infected patients compared to healthy individuals.

These reports suggest that a specific subset of miRNas may participate in HBV replication either as part of a host anti-HBV defense or as viral strategy to exploit or evade the RISC machinery.From this, we examined serum miRNa expression in chronic HBV and healthy individuals and found a specific subset of miRNas thar are over-expressed in HBV- positive patients in which miR-122 was strongly up-regulated.