干扰素刺激基因15在人类免疫缺陷病毒感染中作用的研究进展

随着有效的联合抗反转录病毒疗法(combination antiretroviral therapy,cART)的普及,人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者的生存期逐步延长。这一过程中,HIV感染者自身免疫反应对免疫系统功能的恢复也发挥了至关重要的作用。HIV感染激活干扰素信号通路,诱导干扰素刺激基因(interferon-stimulated gene,ISG)上调表达,从而发挥抗病毒作用。其中,类泛素蛋白ISG15在HIV感染者中显著上调,通过ISG化抑制HIV颗粒的出芽和释放;而HIV的非结构蛋白则通过干扰ISG化过程或结合干扰素信号通路关键分子,逆转ISG15对病毒的抑制作用。本文从ISG15的生物学特性、在不同细胞亚群中的表达、抗病毒功能及病毒逃逸机制等方面进行综述,为进一步解析ISG15在HIV感染中扮演的角色、探索如何获得以抗HIV感染宿主因子为契机的治疗策略提供了思路。

Role of interferon-stimulated gene 15 in human immunodeficiency virus infection

The survival period of human immunodeficiency virus (HIV)-infected patients has been gradually extended due to effective combination antiretroviral therapy. The immune response of HIV-infected individuals also plays a crucial role in the recovery of the host’s immune system during viral suppression phase. HIV infection activates the interferon signaling pathway and induces up-regulated expression of interferon-stimulated genes (ISGs) that exert antiviral effects. The ubiquitin-like protein ISG15 is one of the most significantly up-regulated host factors in HIV-infected patients, inhibiting the budding and release of HIV viral particles through ISGylation, while the non-structural proteins of HIV interfere with ISGylation process or bind to key molecules of interferon signaling pathways to reverse the inhibitory effect of ISG15 on the virus. Herein we review the biological characteristics of ISG15, its expression in different cell populations, antiviral effects, and mechanism of escaping from the host immune restriction, in order to further understand the role of ISG15 in HIV infection, and to explore the opportunities of functional cure of HIV-infected patients with the strategies using host factors.