title: The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells.
abstract: The JAK2 inhibitor AZD1480 has been reported to inhibit La protein expression. We previously demonstrated that the inhibition of La expression could inhibit hepatitis A virus (HAV) internal ribosomal entry-site (IRES)-mediated translation and HAV replication in vitro. In this study, we analyzed the effects of AZD1480 on HAV IRES-mediated translation and replication. HAV IRES-mediated translation in COS7-HAV-IRES cells was inhibited by 0.1-1 μM AZD1480, a dosage that did not affect cell viability. Results showed a significant reduction in intracellular HAV HA11-1299 genotype IIIA RNA levels in Huh7 cells treated with AZD1480. Furthermore, AZD1480 inhibited the expression of phosphorylated-(Tyr-705)-signal transducer and activator of transcription 3 (STAT3) and La in Huh7 cells. Therefore, we propose that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein.
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: kandat-cib@umin.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.affiliation: Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Haga
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shirasawa
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, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006506:Hepatitis A / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D030041:Hepatitis A virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C545606:AZD 1480; D000998:Antiviral Agents; D011720:Pyrazoles; D011743:Pyrimidines; D012367:RNA, Viral; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2
keywords: AZD1480; HAV; IRES; La; STAT3