IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain.
Sorbonne Université, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
Front Immunol. 2018 Dec 6;9:2876. doi: 10.3389/fimmu.2018.02876. eCollection 2018.
Antiviral restriction factors are host cellular proteins that constitute a first line of defense blocking viral replication and propagation. In addition to interfering at critical steps of the viral replication cycle, some restriction factors also act as innate sensors triggering innate responses against infections. Accumulating evidence suggests an additional role for restriction factors in promoting antiviral cellular immunity to combat viruses. Here, we review the recent progress in our understanding on how restriction factors, particularly APOBEC3G, SAMHD1, Tetherin, and TRIM5α have the cell-autonomous potential to induce cellular resistance against HIV-1 while promoting antiviral innate and adaptive immune responses. Also, we provide an overview of how these restriction factors may connect with protein degradation pathways to modulate anti-HIV-1 cellular immune responses, and we summarize the potential of restriction factors-based therapeutics. This review brings a global perspective on the influence of restrictions factors in intrinsic, innate, and also adaptive antiviral immunity opening up novel research avenues for therapeutic strategies in the fields of drug discovery, gene therapy, and vaccines to control viral infections.
抗病毒限制因子是宿主细胞蛋白，构成了阻止病毒复制和传播的第一道防线。除了在病毒复制周期的关键步骤中发挥干扰作用外，一些限制因子还作为先天传感器，针对感染触发先天反应。越来越多的证据表明，限制因子在促进抗病毒细胞免疫以对抗病毒方面具有额外的作用。在这里，我们回顾了最近在理解限制因子（特别是 APOBEC3G、SAMHD1、Tetherin 和 TRIM5α）如何具有细胞自主潜力诱导细胞抵抗 HIV-1 的同时促进抗病毒先天和适应性免疫反应方面的最新进展。我们还概述了这些限制因子如何与蛋白降解途径连接以调节抗 HIV-1 细胞免疫反应，并总结了基于限制因子的治疗方法的潜力。这篇综述从整体上探讨了限制因子在固有、先天和适应性抗病毒免疫中的影响，为药物发现、基因治疗和疫苗等领域的治疗策略开辟了新的研究途径，以控制病毒感染。
