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

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Eukaryotic cells constantly expel a variety of small vesicles that are loaded with proteins, nucleic acids and other small compounds that were produced inside the cell. One particular kind of vesicle is called exosome. Exosomes are initially located in multivesicular compartments inside cells and are docked at the cell surface membrane by the small GTPase Rab27a. In the liver, high expression of Rab27a correlates with the development of hepatocellular carcinoma, suggesting a high trafficking capacity for exosomes. Also, it has been shown that hepatitis C virus (HCV) can spread from cell to cell via exosomes. We discovered that Rab27a abundance affects HCV virion abundance that independent from its role in exosome secretion. The presence of Rab27a in membrane-enriched replication complexes and nearby lipid droplets points to functions of Rab27a in the viral life cycle. Depletion of Rab27a resulted in a lower abundance of the liver-specific microRNA miR-122. It is known that two molecules of miR-122 form an oligomeric complex with the 5’ end of the viral RNA leading to protection of the viral RNA against cellular nucleases. However, we show that the Rab27a-mediated loss of miR-122 was independent of its role in protecting the viral RNA, very likely by the downregulation of a cellular inhibitor of HCV gene expression. These findings argue for novel, hitherto undetected roles for miR-122 in the viral life cycle.

Vyšlo v časopise: Supporting Role for GTPase Rab27a in Hepatitis C Virus RNA Replication through a Novel miR-122-Mediated Effect. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005116
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005116

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