title: Hepatitis C virus NS4A and NS4B proteins suppress translation in vivo.
abstract: Many viruses can inhibit protein synthesis in their host cells by targeting translation ("translational shutoff"). There are few reports on the effects of hepatitis C virus (HCV) infection on protein synthesis, because of the lack of a reproducible tissue culture system for HCV. In this study, the influence of seven HCV proteins (core, NS2, NS3, NS4A, NS4B, NS5A, NS5B) on protein synthesis was examined using a reporter assay. In addition, it was determined whether the HCV proteins inhibit protein synthesis via transcription or translation using an RNase protection assay and the effect of HCV proteins on translation from the HCV internal ribosome entry site (IRES) was also examined using a bicistronic reporter. Of the seven HCV proteins, NS4A and NS4B proteins inhibited cellular protein synthesis by targeting the process of translation. They also inhibited translation from the HCV IRES. Moreover, NS4A protein, induced under the control of doxycycline, inhibited the proliferation of HeLa cells. In conclusion, HCV NS4A and NS4B proteins have an effect of translational inhibition. This novel function may be involved in HCV infection and help its survival in host cells.
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Suzane Kioko
authors.initials: SK
authors.lastname: Ono-Nita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D012260:Ribonucleases; D012270:Ribosomes / Q000378:metabolism; D014407:Tumor Cells, Cultured; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
chemical_list: C093542:NS4 protein, hepatitis C virus; D011506:Proteins; D017361:Viral Nonstructural Proteins; D012260:Ribonucleases