Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Eur J Cell Biol. 2011 Jun-Jul;90(6-7):495-504. doi: 10.1016/j.ejcb.2010.10.016. Epub 2010 Dec 21.
Viral Interleukin-6 (vIL-6) is encoded by Human herpes virus 8 (HHV8), also known as Kaposi's sarcoma (KS)-associated herpes virus (KSHV). HHV8 infection is found in patients with KS, primary effusion lymphoma (PEL) and plasma cell-type of multicentric Castleman's disease (MCD), with a high incidence observed in HIV infected individuals. vIL-6 shares about 25% identity with its human counterpart. Human IL-6 (hIL-6) binds to the human IL-6 receptor (hIL-6R) and the hIL-6/hIL-6R complex associates with the signaling receptor subunit gp130. Upon dimerization of gp130 intracellular signaling is initiated. All cells in the body express gp130 but only some cell types express the hIL-6R. Human IL-6 does not stimulate cells, which do not express hIL-6R. However, a naturally occurring soluble form of the hIL-6R (shIL-6R) can bind hIL-6 and the complex of hIL-6/shIL-6R can stimulate cells, which only express gp130 but no hIL-6R. This process, which has been named trans-signaling, leads to a dramatic increase in the spectrum of hIL-6 target cells during inflammation and cancer. vIL-6, in contrast to hIL-6, can directly bind to and activate gp130 without the need of the hIL-6R. Therefore, at least in theory, vIL-6 can stimulate every cell in the human body. This review highlights the properties of vIL-6 regarding structural features, implications for pathophysiology, and strategies of neutralization. Furthermore, mechanisms of activation of gp130 by hIL-6, vIL-6, and by forced dimerization will be discussed.
病毒白细胞介素 6（vIL-6）由人类疱疹病毒 8（HHV8）编码，也称为卡波西肉瘤（KS）相关疱疹病毒（KSHV）。HHV8 感染见于卡波西肉瘤、原发性渗出性淋巴瘤（PEL）和浆细胞型多中心 Castleman 病（MCD）患者，在 HIV 感染者中观察到发病率较高。vIL-6 与人源白细胞介素 6（hIL-6）有大约 25%的同源性。人类白细胞介素 6（hIL-6）与人类白细胞介素 6 受体（hIL-6R）结合，hIL-6/hIL-6R 复合物与信号转导受体亚基 gp130 结合。gp130 二聚化后启动细胞内信号转导。体内所有细胞均表达 gp130，但只有某些细胞类型表达 hIL-6R。人类白细胞介素 6 不能刺激不表达 hIL-6R 的细胞。然而，hIL-6 的一种天然存在的可溶性形式（shIL-6R）可以与 hIL-6 结合，hIL-6/shIL-6R 复合物可以刺激仅表达 gp130 而不表达 hIL-6R 的细胞。这个过程被命名为转信号，导致在炎症和癌症期间 hIL-6 靶细胞的范围显著增加。与 hIL-6 相反，vIL-6 可以直接与 gp130 结合并激活它，而不需要 hIL-6R。因此，至少在理论上，vIL-6 可以刺激人体的每一个细胞。本综述强调了 vIL-6 在结构特征、对病理生理学的影响以及中和策略方面的特性。此外，还将讨论 hIL-6、vIL-6 和强制二聚化激活 gp130 的机制。
