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Hepatitis c virus infection induces the expression of amphiregulin, a factor related to the activation of cellular survival pathways and required for efficient viral assembly
Pei, Rongjuan1,2,3; Chen, Honghe1,3; Lu, Lu1; Zhu, Wandi1,3; Beckebaum, Susanne4; Cicinnati, Vito4; Lu, Mengji2; Chen, Xinwen1
刊名Journal of general virology
2011-10-01
卷号92页码:2237-2248
ISSN号0022-1317
DOI10.1099/vir.0.032581-0
通讯作者Chen, xinwen(chenxw@wh.iov.cn)
英文摘要Amphiregulin (areg) is a ligand of the epidermal growth factor (egf) receptor and may play a role in the development of cirrhosis and hepatocellular carcinoma in patients infected with hepatitis c virus (hcv). areg showed an enhanced expression in hcv-infected human hepatoma cells according to gene array analysis. therefore, we addressed the question about the role of areg in hcv infection. areg expression level was elevated in hepatoma cells containing a subgenomic hcv replicon or infected by hcv. using a reporter assay, areg promoter activity was found to be upregulated upon hcv infection. the enhanced areg expression in hepatoma cells was partly caused by dsrnas, hcv ns3 protein and autocrine stimulation. areg was able to activate cellular signalling pathways including erk, akt and p38, promote cell proliferation, and protect cells from hcv-induced cell death. further, knockdown of areg expression increased the efficiency of hcv entry, as proven by hcv pseudoparticles reporter assay. however, the formation and release of infectious hcv particles were reduced by areg silencing with a concomitant accumulation of intracellular hcv rna pool, indicating that the assembly and release of hcv progeny may require areg expression. blocking the mapk-erk pathway by u0126 in huh7.5.1 cells had a similar effect on hcv replication. in conclusion, hcv infection leads to an increase in areg expression in hepatocytes. areg expression is essential for efficient hcv assembly and virion release. due to the activation of the cellular survival pathways, areg may counteract hcv-induced apoptosis of infected hepatocytes and facilitate the development of liver cirrhosis and hepatocellular carcinoma.
WOS关键词RECEPTOR-LIGAND AMPHIREGULIN ; GROWTH-FACTOR ; GENE-EXPRESSION ; BREAST-CANCER ; HOST FACTORS ; REPLICATION ; CELLS ; PROTEIN ; SCREEN ; TRAFFICKING
WOS研究方向Biotechnology & Applied Microbiology ; Virology
WOS类目Biotechnology & Applied Microbiology ; Virology
语种英语
出版者SOC GENERAL MICROBIOLOGY
WOS记录号WOS:000295856000002
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2375942
专题武汉病毒研究所
通讯作者Chen, Xinwen
作者单位1.Chinese Acad Sci, Wuhan Inst Virol, Wuhan, Peoples R China
2.Univ Hosp Essen, Inst Virol, Essen, Germany
3.Chinese Acad Sci, Grad Univ, Beijing, Peoples R China
4.Univ Hosp Essen, Dept Gastroenterol & Hepatol, Essen, Germany
推荐引用方式
GB/T 7714
Pei, Rongjuan,Chen, Honghe,Lu, Lu,et al. Hepatitis c virus infection induces the expression of amphiregulin, a factor related to the activation of cellular survival pathways and required for efficient viral assembly[J]. Journal of general virology,2011,92:2237-2248.
APA Pei, Rongjuan.,Chen, Honghe.,Lu, Lu.,Zhu, Wandi.,Beckebaum, Susanne.,...&Chen, Xinwen.(2011).Hepatitis c virus infection induces the expression of amphiregulin, a factor related to the activation of cellular survival pathways and required for efficient viral assembly.Journal of general virology,92,2237-2248.
MLA Pei, Rongjuan,et al."Hepatitis c virus infection induces the expression of amphiregulin, a factor related to the activation of cellular survival pathways and required for efficient viral assembly".Journal of general virology 92(2011):2237-2248.
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