title: Hepatitis A virus (HAV) proteinase 3C inhibits HAV IRES-dependent translation and cleaves the polypyrimidine tract-binding protein.
abstract: Hepatitis A virus (HAV) infection is still an important issue worldwide. A distinct set of viruses encode proteins that enhance viral cap-independent translation initiation driven by an internal ribosome entry site (IRES) and suppress cap-dependent host translation. Unlike cytolytic picornaviruses, replication of HAV does not cause host cell shut off, and it has been questioned whether HAV proteins interfere with its own and/or host translation. HAV proteins were coexpressed in Huh-7 cells with reporter genes whose translation was initiated by either cap-dependent or cap-independent mechanisms. Among the proteins tested, HAV proteinase 3C suppressed viral IRES-dependent translation. Furthermore, 3C cleaved the polypyrimidine tract-binding protein (PTB) whose interaction with the HAV IRES had been demonstrated previously. The combined results suggest that 3C-mediated cleavage of PTB might be involved in down-regulation of viral translation to give way to subsequent viral genome replication.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan. kandat-cib@umin.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kanda
authors.forename: V
authors.initials: V
authors.lastname: Gauss-Müller
authors.forename: S
authors.initials: S
authors.lastname: Cordes
authors.forename: R
authors.initials: R
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Okitsu
authors.forename: W
authors.initials: W
authors.lastname: Shuang
authors.forename: S
authors.initials: S
authors.lastname: Nakamoto
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: F
authors.initials: F
authors.lastname: Imazeki
authors.forename: O
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000086042:3C Viral Proteases; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D017930:Genes, Reporter; D030041:Hepatitis A virus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D014176:Protein Biosynthesis; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; D038941:Polypyrimidine Tract-Binding Protein; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases