Jiang Xia, Kanda Tatsuo, Nakamoto Shingo, Saito Kengo, Nakamura Masato, Wu Shuang, Haga Yuki, Sasaki Reina, Sakamoto Naoya, Shirasawa Hiroshi, Okamoto Hiroaki, Yokosuka Osamu
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Biochem Biophys Res Commun. 2015 Mar 20;458(4):908-12. doi: 10.1016/j.bbrc.2015.02.058. Epub 2015 Feb 19.
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.
据报道，JAK2抑制剂AZD1480可抑制La蛋白表达。我们之前证明，抑制La表达可在体外抑制甲型肝炎病毒（HAV）内部核糖体进入位点（IRES）介导的翻译及HAV复制。在本研究中，我们分析了AZD1480对HAV IRES介导的翻译和复制的影响。在COS7-HAV-IRES细胞中，0.1-1μM的AZD1480可抑制HAV IRES介导的翻译，该剂量不影响细胞活力。结果显示，用AZD1480处理的Huh7细胞中，细胞内HAV HA11-1299 IIIA型基因型RNA水平显著降低。此外，AZD1480可抑制Huh7细胞中磷酸化-（酪氨酸-705）-信号转导和转录激活因子3（STAT3）及La的表达。因此，我们认为AZD1480可通过抑制La蛋白来抑制HAV IRES活性及HAV复制。
