Viral IL-6-induced cell proliferation and immune evasion of interferon activity
Viral IL-6-induced cell proliferation and immune evasion of interferon activity
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DOI：
10.1126/science.1074883
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发表时间：
2002-11-15
期刊：
影响因子：
56.9
通讯作者：
Moore, PS
中科院分区：
文献类型：
--
作者：
Chatterjee, M;Osborne, J;Moore, PS
感染卡波西肉瘤相关疱疹病毒的淋巴瘤细胞自分泌依赖于病毒源性白细胞介素 6 (IL-6)，但不依赖于细胞 IL-6。在病毒感染期间，宿主细胞诱导抗病毒因子干扰素 (IFN) 上调 p21、启动细胞周期停滞并抑制病毒复制。然而，病毒 IL-6 会阻断 IFN 信号传导。存在一种病毒转录程序，其中只有病毒 IL-6 基因被 IFN-α 直接激活，从而允许病毒通过感知和响应细胞内 IFN 信号传导水平来改变其细胞环境。人类细胞因子无法模拟这种效应，因为 IFN-α 会下调 IL-6 受体 gp80。病毒IL-6通过直接结合gp130转导分子绕过gp80调节检查点，导致肿瘤细胞自分泌依赖病毒细胞因子进行增殖和存活。
Lymphoma cells infected with Kaposi's sarcoma-associated herpesvirus are autocrine dependent on virus-derived interleukin-6 (IL-6), but not on cellular IL-6. During viral infection, host cells induce the antiviral factor interferon (IFN) to up-regulate p21, initiate cell cycle arrest, and inhibit virus replication. Viral IL-6, however, blocks IFN signaling. A viral transcriptional program exists in which only the viral IL-6 gene is directly activated by IFN-alpha, allowing the virus to modify its cellular environment by sensing and responding to levels of intracellular IFN signaling. The human cytokine cannot mimic this effect because IFN-alpha down-regulates the IL-6 receptor, gp80. Viral IL-6 bypasses the gp80 regulatory checkpoint by binding directly to the gp130 transducer molecule, resulting in tumor cell autocrine dependence on the viral cytokine for proliferation and survival.