Hepatitis B Virus-Induced Calreticulin Protein Is Involved in IFN Resistance
Hepatitis B Virus-Induced Calreticulin Protein Is Involved in IFN Resistance
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乙型肝炎病毒诱导的钙网蛋白参与干扰素抵抗
DOI：
10.4049/jimmunol.1103405
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Zhu, Ying
中科院分区：
文献类型：
--
作者：
Yue, Xin;Wang, Hui;Zhao, Fanpeng;Liu, Shi;Wu, Jianguo;Ren, Wendan;Zhu, Ying
干扰素-α是一种广泛用于治疗乙肝病毒感染的药物，由病毒和/或宿主因素引起的干扰素耐药是目前临床上一个具有挑战性的问题。更好地了解干扰素免疫疗法治疗病毒感染的分子机制将在临床上非常有益，具有巨大的临床意义。钙网蛋白(CRT)是一种内质网腔内钙结合伴侣，参与钙稳态的调节、新合成蛋白质的折叠等多种细胞功能。然而，对CRT在乙肝病毒感染中的作用知之甚少。在这项研究中，我们观察到与健康人相比，乙肝患者血清和PBMCs中CRT的表达水平较高。乙肝病毒在转录水平上调CRT的表达。进一步的研究表明，乙肝病毒诱导的CRT通过拮抗干扰素途径增强了乙肝病毒的复制。CRT通过减少干扰素调节因子-7的核转位而抑制内源性干扰素-α的产生，但不能抑制干扰素调节因子-3的核转位。此外，CRT还通过抑制STAT1的磷酸化和降低两种干扰素-α下游效应蛋白激酶R和2‘，5’-寡腺苷合成酶的表达来抑制干扰素-α的抗病毒活性。我们的研究结果为了解乙肝病毒感染的发病机制提供了新的见解，并可能为抗乙肝病毒治疗提供潜在的靶点。
IFN-α is a widely used treatment for hepatitis B virus (HBV) infection, and IFN resistance caused by viral and/or host factors is currently a challenging clinical problem. A better understanding of the molecular mechanisms underlying IFN immunotherapy in the treatment of viral infection would be very beneficial clinically and is of immense clinical importance. Calreticulin (CRT) is an endoplasmic reticulum luminal calcium-binding chaperone that is involved in the regulation of calcium homoeostasis, the folding of newly synthesized proteins, and many other cellular functions. However, little is known about the role of CRT in HBV infection. In this study, we observed high levels of CRT expression in the sera and PBMCs of patients with HBV relative to those of healthy individuals. HBV upregulated the expression of CRT at the transcriptional level. Further investigation showed that HBV-induced CRT enhanced HBV replication by antagonizing the IFN pathway. CRT suppressed the production of endogenous IFN-α by reducing the nuclear translocation of IFN regulatory factor-7 but not IFN regulatory factor-3. Furthermore, CRT also suppressed the antiviral activity of IFN-α by inhibiting the phosphorylation of STAT1 and decreasing the expression of two IFN-α downstream effectors, protein kinase R and 2', 5′-oligoadenylate synthetase. Our results offer new insights into the pathogenesis of HBV infection and may provide potential targets for anti-HBV therapy.
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影响因子：
6.4
作者：
P. Knekt;R. Järvinen;J. Dich;T. Hakulinen
通讯作者：
P. Knekt;R. Järvinen;J. Dich;T. Hakulinen
DOI：
10.1038/sj.jidsymp.5650011
发表时间：
2006-09-01
影响因子：
--
作者：
Gold, Leslie I.;Rahman, Mohammad;Cadacio, Caprice L.
通讯作者：
Cadacio, Caprice L.
DOI：
10.1016/s0021-9258(17)44794-6
发表时间：
1990-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
I. Marié;J. Svab;N. Robert;J. Galabru;A. Hovanessian
通讯作者：
I. Marié;J. Svab;N. Robert;J. Galabru;A. Hovanessian
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
影响因子：
5.3
作者：
R. Lin;Y. Mamane;J. Hiscott
通讯作者：
R. Lin;Y. Mamane;J. Hiscott