title: MEK5/ERK5/mef2: a novel signaling pathway affected by hepatitis C virus non-enveloped capsid-like particles.
abstract: Hepatitis C virus (HCV) is an RNA positive strand virus, member of the Flaviviridae family. The viral particle is composed of a capsid containing the genome, surrounded by E1 and E2 proteins, however different forms of viral particles have been observed including non-enveloped particles. Previous reports have proposed that hepatitis C non-enveloped capsid-like particles (HCVne) enter cells of hepatic origin via clathrin-mediated endocytosis, during which different signaling events occur. In this report we show that HCVne particles are capable of inducing the recently discovered ERK5 pathway, in a dose dependent way. The ERK5 pathway can be activated by growth factors and other extracellular signals. This specific activation occurs through a well characterized upstream kinase, MEK5, and is capable of inducing gene regulation of mef2. In contrast, when HCV core structural and NS5A non-structural proteins were expressed endogenously no activation of this pathway was detected. These cell signaling events could be of critical importance and might give clues for the elucidation of cellular manifestations associated with HCV infection.
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Katsarou
authors.forename: Panagiota
authors.initials: P
authors.lastname: Tsitoura
authors.forename: Urania
authors.initials: U
authors.lastname: Georgopoulou
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000502:physiology; D006801:Humans; D026161:MADS Domain Proteins / Q000378:metabolism* / Q000502:physiology; D048671:MAP Kinase Kinase 5 / Q000378:metabolism* / Q000502:physiology; D064326:MEF2 Transcription Factors; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D018006:Myogenic Regulatory Factors / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D018411:Spodoptera; D014758:Viral Core Proteins / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000494:pharmacology; D014771:Virion / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D036022:Capsid Proteins; D026161:MADS Domain Proteins; D048671:MAP Kinase Kinase 5; D064326:MEF2 Transcription Factors; D048054:Mitogen-Activated Protein Kinase 7; D018006:Myogenic Regulatory Factors; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C578035:MEF2A protein, human; C482563:MAP2K5 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase