Hepatitis C virus protects human B lymphocytes from Fas-mediated apoptosis via E2-CD81 engagement.
Hepatitis C virus protects human B lymphocytes from Fas-mediated apoptosis via E2-CD81 engagement.
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丙型肝炎病毒通过 E2-CD81 参与保护人类 B 淋巴细胞免受 Fas 介导的细胞凋亡
DOI：
10.1371/journal.pone.0018933
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发表时间：
2011-04-19
期刊：
影响因子：
3.7
通讯作者：
Qi Z
中科院分区：
文献类型：
--
作者：
Chen Z;Zhu Y;Ren Y;Tong Y;Hua X;Zhu F;Huang L;Liu Y;Luo Y;Lu W;Zhao P;Qi Z
HCV 感染通常与 B 细胞调节控制紊乱和中和抗体延迟出现有关。 CD81 是 HCV 的细胞受体，可以与 HCV 包膜蛋白 2 (E2) 结合。 CD81 还参与形成 B 细胞共刺激复合物。为了研究HCV是否通过E2-CD81接合影响B细胞活化和免疫功能，本文用HCV E2蛋白处理人伯基特淋巴瘤细胞系Raji细胞和原代人B淋巴细胞（PHB）并细胞培养产生HCV颗粒（HCVcc），然后测定相关细胞表型。结果表明，E2和HCVcc均触发IκBα磷酸化，增强抗凋亡Bcl-2家族蛋白的表达，并保护Raji细胞和PHB细胞免受Fas介导的死亡。此外，E2蛋白和HCVcc均增加共刺激分子CD80、CD86和CD81本身的表达，并减少补体受体CD21的表达。这些效果取决于细胞表面上的 E2-CD81 相互作用，因为 CD81 沉默的 Raji 细胞对两种处理均没有反应。失去CD81结合活性的E2突变体不能触发Raji细胞和PHB细胞的反应。该效应与HCV在细胞中的复制无关，因为HCV假颗粒(HCVpp)和HCVcc未能感染Raji细胞。因此，E2-CD81 结合可能导致 HCV 相关 B 细胞淋巴增殖性疾病和中和抗体产生不足。
HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2). CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB) were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc), and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp) and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production.
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DOI：
10.1084/jem.20090766
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fafi-Kremer S;Fofana I;Soulier E;Carolla P;Meuleman P;Leroux-Roels G;Patel AH;Cosset FL;Pessaux P;Doffoël M;Wolf P;Stoll-Keller F;Baumert TF
通讯作者：
Baumert TF
影响因子：
5.4
作者：
Flint, M;Dubuisson, J;McKeating, JA
通讯作者：
McKeating, JA
影响因子：
158.5
作者：
Hermine, O;Lefrère, F;Troussard, X
通讯作者：
Troussard, X
影响因子：
3.8
作者：
Baré, P;Massud, I;Ares, BR
通讯作者：
Ares, BR
影响因子：
3.5
作者：
Hu, Y;Shahidi, A;Hirshfield, I
通讯作者：
Hirshfield, I