Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
Cytokine Growth Factor Rev. 2018 Apr;40:13-18. doi: 10.1016/j.cytogfr.2018.02.002. Epub 2018 Feb 13.
Type I interferons (IFN), which are immediately induced after most virus infections, are central for direct antiviral immunity and link innate and adaptive immune responses. However, several viruses have evolved strategies to evade the IFN response by preventing IFN induction or blocking IFN signaling pathways. Thus, therapeutic application of exogenous type I IFN or agonists inducing type I IFN responses are a considerable option for future immunotherapies against chronic viral infections. An important part of the type I IFN family are 12 IFNα subtypes, which all bind the same receptor, but significantly differ in their biological activities. Up to date only one IFNα subtype (IFNα2) is being used in clinical treatment against chronic virus infections, however its therapeutic success rate is rather limited, especially during Human Immunodeficiency Virus (HIV) infection. Recent studies addressed the important question if other IFNα subtypes would be more potent against retroviral infections in in vitro and in vivo experiments. Indeed, very potent IFNα subtypes were defined and their antiviral and immunomodulatory properties were characterized. In this review we summarize the recent findings on the role of individual IFNα subtypes during HIV and Simian Immunodeficiency Virus infection. This includes their induction during HIV/SIV infection, their antiretroviral activity and the regulation of immune response against HIV by different IFNα subtypes. The findings might facilitate novel strategies for HIV cure or functional cure studies.
I 型干扰素（IFN）在大多数病毒感染后立即被诱导产生，对于直接抗病毒免疫至关重要，将先天免疫和适应性免疫反应联系起来。然而，一些病毒已经进化出了通过阻止 IFN 诱导或阻断 IFN 信号通路来逃避 IFN 反应的策略。因此，外源性 I 型 IFN 或诱导 I 型 IFN 反应的激动剂的治疗应用是未来针对慢性病毒感染的免疫治疗的一个重要选择。I 型 IFN 家族的一个重要部分是 12 种 IFNα 亚型，它们都结合相同的受体，但在生物学活性上有很大的差异。迄今为止，只有一种 IFNα 亚型（IFNα2）用于临床治疗慢性病毒感染，但它的治疗成功率相当有限，特别是在人类免疫缺陷病毒（HIV）感染期间。最近的研究解决了一个重要问题，即其他 IFNα 亚型在体外和体内实验中是否对逆转录病毒感染更有效。事实上，已经确定了非常有效的 IFNα 亚型，并对其抗病毒和免疫调节特性进行了表征。在这篇综述中，我们总结了最近关于 HIV 和猴免疫缺陷病毒感染期间个体 IFNα 亚型作用的研究结果。这包括它们在 HIV/SIV 感染期间的诱导、它们的抗逆转录病毒活性以及不同 IFNα 亚型对 HIV 免疫反应的调节。这些发现可能为 HIV 治愈或功能性治愈研究提供新的策略。
