Differential regulation of SOCS-1 signalling in B and T lymphocytes by hepatitis C virus core protein
Differential regulation of SOCS-1 signalling in B and T lymphocytes by hepatitis C virus core protein
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DOI：
10.1111/j.1365-2567.2008.02829.x
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发表时间：
2008-10-01
期刊：
影响因子：
6.4
通讯作者：
Moorman, Jonathan
中科院分区：
文献类型：
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作者：
Yao, Zhi Qiang;Prayther, Deborah;Moorman, Jonathan
丙型肝炎病毒(HCV)感染具有强烈的慢性化倾向、自身免疫现象和淋巴肿大，在持续性病毒感染过程中支持淋巴细胞调节失调的作用。我们已经证明，丙型肝炎病毒核心蛋白通过与补体受体gC1qR相互作用来抑制T细胞功能。在此，我们进一步报道，B细胞也表达可与丙型肝炎病毒核心蛋白结合的gC1qR。重要的是，利用流式细胞术，我们证明了通过丙型肝炎病毒核心-gC1qR相互作用对B和T淋巴细胞的不同调节，T细胞中CD69激活的下调，而B细胞中CD69激活和细胞增殖的上调。经丙型肝炎病毒核心治疗后，CD8(+)T细胞产生的干扰素-γ减少，CD20(+)B细胞免疫球蛋白M和免疫球蛋白G的产生增加，共刺激和趋化因子受体CD86(B7-2)、CD154(CD40L)和CD195(CCR5)的表达增加。最后，我们利用实时逆转录-聚合酶链式反应显示了细胞因子信号转导抑制因子-1(SOCS-1)的下调，同时伴随着信号转导和转录激活因子-1(STAT1)的磷酸化上调，以响应丙型肝炎病毒核心蛋白，而在丙型肝炎病毒核心处理的T细胞中观察到相反的模式。这项研究证明了丙型肝炎病毒核心对B和T淋巴细胞的不同调节，并支持在持续的丙型肝炎病毒感染过程中发生淋巴细胞调节失调的机制。
Hepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity, autoimmune phenomena and lymphomagenesis, supporting a role for lymphocyte dysregulation during persistent viral infection. We have shown that HCV core protein inhibits T-cell functions through interaction with a complement receptor, gC1qR. Here, we further report that B cells also express gC1qR that can be bound by HCV core protein. Importantly, using flow cytometry, we demonstrated differential regulation of B and T lymphocytes by the HCV core-gC1qR interaction, with down-regulation of CD69 activation in T cells but up-regulation of CD69 activation and cell proliferation in B cells. HCV core treatment led to decreased interferon-gamma production in CD8(+) T cells but to increased immunoglobulin M and immunoglobulin G production as well as cell surface expression of costimulatory and chemokine receptors, including CD86 (B7-2), CD154 (CD40L) and CD195 (CCR5), in CD20(+) B cells. Finally, we showed down-regulation of suppressor of cytokine signalling-1 (SOCS-1) using real-time reverse transcription-polymerase chain reaction, accompanied by up-regulation of signal transducer and activator of transcription-1 (STAT1) phosphorylation in B cells in response to HCV core protein, with the opposite pattern observed in HCV core-treated T cells. This study demonstrates differential regulation of B and T lymphocytes by HCV core and supports a mechanism by which lymphocyte dysregulation occurs in the course of persistent HCV infection.