IFN-CSP inhibiting hepatitis B virus in HepG2.2.15 cells involves JAK-STAT signal pathway.
IFN-CSP inhibiting hepatitis B virus in HepG2.2.15 cells involves JAK-STAT signal pathway.
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DOI：
10.1155/2015/959684
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发表时间：
2015
影响因子：
--
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Lu X;Wang J;Jin X;Huang Y;Zeng W;Zhu J
病毒性肝炎患者频繁、大剂量使用干扰素会产生多种副作用。本课题组在前期研究中成功设计并表达了疟原虫I区肽与IFNα2b结合的新型肝靶向干扰素（IFN CSP）。这种靶向将IFNα2b特异性靶向肝脏，从而减少不良事件。本研究进一步研究了重组IFN-CSP在HepG2.2.15细胞中的抗HBV作用及其分子机制。用酶联免疫吸附试验（ELISA）检测培养上清中的B肝炎表面抗原（HBsAg）和乙型肝炎e抗原（HBeAg）。实时荧光定量PCR检测HBV-DNA。免疫荧光和Western blot分析HBV核心蛋白。采用逆转录PCR和Western blot检测细胞内信号转导和反式激活因子1（STAT 1）、STAT 2、干扰素调节因子9（IRF-9）和2′-5′-寡腺苷酸合成酶1（OAS 1）的表达。结果表明，IFN-CSP有效地抑制HepG2.2.15细胞中HBsAg和HBeAg的分泌、HBV-DNA复制和HBV核心蛋白的表达。其抗HBV机制涉及激活JAK-STAT信号通路和增加抗HBV蛋白OAS的表达。IFN-CSP可替代IFNα2b用于抗HBV治疗。
Frequent and high-dose administration of interferon to patients with viral hepatitis results in various side effects. In our previous study, a novel liver-targeting interferon (IFN-CSP) combining Plasmodium region I peptide with IFNα2b was successfully designed and expressed in the Escherichia coli expression systems. This targeting would target the IFNα2b specifically to the liver, thus reducing the adverse events. In the present study, we further investigated the anti-HBV effects and molecular mechanisms of recombinant IFN-CSP in HepG2.2.15 cell line. Hepatitis B surface antigen (HBsAg) and HBe antigen (HBeAg) in the culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA). HBV-DNA was measured by real-time quantitative PCR. HBV core protein was assayed by immunofluorescent and western blot analysis. The expressions of signal transducers and transactivator 1 (STAT1), STAT2, IFN regulatory factor 9 (IRF-9), and 2′-5′-oligoadenylate synthetase 1 (OAS1) were investigated by the reverse transcription PCR and western blot analysis. Results indicate IFN-CSP efficiently inhibited HBsAg and HBeAg secretion, HBV-DNA replication, and HBV core protein expression in HepG2.2.15 cells. The anti-HBV mechanisms involve activation of JAK-STAT signaling and increase of the anti-HBV protein OAS expression. IFN-CSP could be a good substitute for IFNα2b for anti-HBV treatment.
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DOI：
10.1073/pnas.84.4.1005
发表时间：
1987-02-01
影响因子：
11.1
作者：
SELLS, MA;CHEN, ML;ACS, G
通讯作者：
ACS, G
DOI：
10.1073/pnas.77.9.5507
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
HIRSCHMAN, SZ;PRICE, P;ACS, G
通讯作者：
ACS, G
ISGF3在体外调节干扰素-α抗乙型肝炎病毒活性中的作用
DOI：
10.1111/j.1440-1746.2007.04985.x
发表时间：
2008-11-01
影响因子：
4.1
作者：
Zhang, Quan;Wang, Yan;Cong, Xu
通讯作者：
Cong, Xu
影响因子：
5.8
作者：
Longmuir, Kenneth J.;Haynes, Sherry M.;Baratta, Janie L.;Kasabwalla, Natasha;Robertson, Richard T.
通讯作者：
Robertson, Richard T.
影响因子：
15.9
作者：
Belloni, Laura;Allweiss, Lena;Levrero, Massimo
通讯作者：
Levrero, Massimo