title: Suppression of La antigen exerts potential antiviral effects against hepatitis A virus.
abstract: BACKGROUND
  Despite the development and availability of hepatitis A virus (HAV) vaccine, HAV infection is still a major cause of acute hepatitis that occasionally leads to fatal liver disease. HAV internal ribosomal entry-site (IRES) is one of the attractive targets of antiviral agents against HAV. The aim of the present study is to evaluate the impact of La, one of the cellular proteins, on HAV IRES-mediated translation and HAV replication.
  
  
  RESULTS
  We investigated the therapeutic feasibility of siRNAs specific for cellular cofactors for HAV IRES-mediated translation in cell culture. It was revealed that siRNA against La could inhibit HAV IRES activities as well as HAV subgenomic replication. We also found that the Janus kinase (JAK) inhibitors SD-1029 and AG490, which reduce La expression, could inhibit HAV IRES activities as well as HAV replication.
  
  
  CONCLUSIONS
  Inhibition of La by siRNAs and chemical agents could lead to the efficient inhibition of HAV IRES-mediated translation and HAV replication in cell culture models. La might play important roles in HAV replication and is being exploited as one of the therapeutic targets of host-targeting antivirals.
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.affiliation: Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shirasawa
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Musashimurayama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kiyohara
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Musashimurayama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Musashimurayama, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D020868:Gene Silencing; D016679:Genome, Viral / Q000187:drug effects / Q000235:genetics; D030041:Hepatitis A virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012261:Ribonucleoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics; D014966:Xanthenes / Q000494:pharmacology; D000097585:SS-B Antigen
chemical_list: D001324:Autoantigens; D053612:Janus Kinases; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; D020032:Tyrphostins; D014966:Xanthenes; D000097585:SS-B Antigen; C516783:SD 1029; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide