Hepatitis C virus infection alters P-body composition but is independent of P-body granules.
Processing bodies (P-bodies) are highly dynamic cytoplasmic granules conserved among eukaryotes. They are present under normal growth conditions and contain translationally repressed mRNAs together with proteins from the mRNA decay and microRNA (miRNA) machineries. We have previously shown that the core P-body components PatL1, LSm1, and DDX6 (Rck/p54) are required for hepatitis C virus (HCV) RNA replication; however, how HCV infection affects P-body granules and whether P-body granules per se influence the HCV life cycle remain unresolved issues. Here we show that HCV infection alters P-body composition by specifically changing the localization pattern of P-body components that are required for HCV replication. This effect was not related to an altered expression level of these components and could be reversed by inhibiting HCV replication with a polymerase inhibitor. Similar observations were obtained with a subgenomic replicon that supports only HCV translation and replication, indicating that these early steps of the HCV life cycle trigger the P-body alterations. Finally, P-body disruption by Rap55 depletion did not affect viral titers or HCV protein levels, demonstrating that the localization of PatL1, LSm1, and DDX6 in P-bodies is not required for their function on HCV. Thus, the HCV-induced changes on P-bodies are mechanistically linked to the function of specific P-body components in HCV RNA translation and replication; however, the formation of P-body granules is not required for HCV infection.
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Gemma
G
Pérez-Vilaró
Nicoletta
N
Scheller
Verónica
V
Saludes
Juana
J
Díez
D002460:Cell Line; D003594:Cytoplasmic Granules / Q000737:chemistry*; D053487:DEAD-box RNA Helicases / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis; D014779:Virus Replication
D004268:DNA-Binding Proteins; C464824:LSM1 protein, human; C526510:PATL1 protein, human; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases