title: La autoantigen suppresses IRES-dependent translation of the hepatitis A virus.
abstract: The human RNA-binding protein La, is an essential trans-acting factor in IRES-dependent translation initiation of poliovirus, the prototypic picornavirus. For hepatitis A virus (HAV), an unusual member of this virus family, the role of host proteins in its inefficient translation and slow replication is unclear. Using small interfering RNA in vivo and purified La in vitro, we demonstrate for the first time that La suppresses HAV IRES-mediated translation and replication. We show that La binds specifically to distinct parts of the HAV IRES and that-unlike poliovirus-HAV proteinase 3C does not cleave La. The La-mediated suppression of HAV translation and stimulation of poliovirus translation implies unexpected mechanistic differences between viral IRES elements.
authors.affiliation: Institute of Medical Molecular Biology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Cordes
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kusov
authors.forename: Tilman
authors.initials: T
authors.lastname: Heise
authors.forename: Verena
authors.initials: V
authors.lastname: Gauss-Müller
mesh_terms: D000086042:3C Viral Proteases; D001324:Autoantigens / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism; D030041:Hepatitis A virus / Q000187:drug effects*; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects*; D034622:RNA Interference; D012261:Ribonucleoproteins / Q000378:metabolism / Q000502:physiology*; D012270:Ribosomes / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism; D000097585:SS-B Antigen
chemical_list: D000086042:3C Viral Proteases; D001324:Autoantigens; D003546:Cysteine Endopeptidases; D012261:Ribonucleoproteins; D014764:Viral Proteins; D000097585:SS-B Antigen