Supporting Role for GTPase Rab27a in Hepatitis C Virus RNA Replication through a Novel miR-122-Mediated Effect

摘要: The small GTPase Rab27a has been shown to control membrane trafficking and microvesicle transport pathways, in particular the secretion of exosomes. In liver, high expression correlates with development hepatocellular carcinoma. We discovered that low abundance resulted decreased hepatitis C virus (HCV) RNA protein abundances virus-infected cells. Curiously, both cell-associated extracellular yield depleted cells, suggesting reduced exosome did not cause observed effect. Instead, enhanced viral replication by a mechanism involves liver-specific microRNA miR-122. surrounded lipid droplets was enriched fractions harbor proteins, supporting role for gene expression. depletion miR-122, whereas overexpression miR-122 Rab27a-depleted cells rescued HCV abundance. Because intracellular is binding two molecules extreme 5' end genome, diminished amounts could have caused destabilization RNA. However, carrying mutations on miR-122-binding sites whose stability supported ectopically expressed mimetics compensatory also This result indicates effect does depend formation terminal HCV/miR-122 complexes, but Rab27a-dependent function lifecycle, likely downregulation cellular inhibitor These findings suggest absence results vulnerability only exoribonucleases attack upregulation one more factor inhibit