title: Hepatitis C virus hijacks P-body and stress granule components around lipid droplets.
abstract: The microRNA miR-122 and DDX6/Rck/p54, a microRNA effector, have been implicated in hepatitis C virus (HCV) replication. In this study, we demonstrated for the first time that HCV-JFH1 infection disrupted processing (P)-body formation of the microRNA effectors DDX6, Lsm1, Xrn1, PATL1, and Ago2, but not the decapping enzyme DCP2, and dynamically redistributed these microRNA effectors to the HCV production factory around lipid droplets in HuH-7-derived RSc cells. Notably, HCV-JFH1 infection also redistributed the stress granule components GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1), ataxin-2 (ATX2), and poly(A)-binding protein 1 (PABP1) to the HCV production factory. In this regard, we found that the P-body formation of DDX6 began to be disrupted at 36 h postinfection. Consistently, G3BP1 transiently formed stress granules at 36 h postinfection. We then observed the ringlike formation of DDX6 or G3BP1 and colocalization with HCV core after 48 h postinfection, suggesting that the disruption of P-body formation and the hijacking of P-body and stress granule components occur at a late step of HCV infection. Furthermore, HCV infection could suppress stress granule formation in response to heat shock or treatment with arsenite. Importantly, we demonstrate that the accumulation of HCV RNA was significantly suppressed in DDX6, Lsm1, ATX2, and PABP1 knockdown cells after the inoculation of HCV-JFH1, suggesting that the P-body and the stress granule components are required for the HCV life cycle. Altogether, HCV seems to hijack the P-body and the stress granule components for HCV replication.
authors.affiliation: Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. ariumi@kumamoto-u.ac.jp
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ariumi
authors.forename: Misao
authors.initials: M
authors.lastname: Kuroki
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kushima
authors.forename: Kanae
authors.initials: K
authors.lastname: Osugi
authors.forename: Makoto
authors.initials: M
authors.lastname: Hijikata
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Maki
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000502:physiology*; D017931:DNA Primers; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000502:physiology
chemical_list: D017931:DNA Primers