Bosinger Steven E, Utay Netanya S
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory Vaccine Center Bldg. 3028, Atlanta, GA, 30322, USA,
Curr HIV/AIDS Rep. 2015 Mar;12(1):41-53. doi: 10.1007/s11904-014-0244-6.
Despite over 30 years of research, the contribution of type I interferons (IFN-Is) to both the control of HIV replication and initiation of immunologic damage remains debated. In acute infection, IFN-Is, likely from plasmacytoid dendritic cells (pDCs), activate NK cells and upregulate restriction factors targeting virtually the entire HIV life cycle. In chronic infection, IFN-Is may also contribute to CD4 T cell loss and immune exhaustion. pDCs subsequently infiltrate lymphoid and mucosal tissues, and their circulating populations wane in chronic infection; IFN-I may be produced by other cells. Data from nonhuman primates indicate prompt IFN-I signaling is critical in acute infection. Whereas some studies showed IFN-I administration without combination antiretroviral therapy (cART) is beneficial, others suggest that stimulating or blocking IFN-I signaling in chronic ART-suppressed HIV infection has had positive results. Here, we describe the history of HIV and IFN-I, IFN-I's sources, IFN-I's effects on HIV control and host defense, and recent interventional studies in SIV and HIV infection.
尽管经过30多年的研究，但I型干扰素（IFN-I）在控制HIV复制和引发免疫损伤方面的作用仍存在争议。在急性感染中，IFN-I可能来自浆细胞样树突状细胞（pDC），它可激活自然杀伤细胞并上调几乎针对HIV整个生命周期的限制因子。在慢性感染中，IFN-I也可能导致CD4 T细胞损失和免疫耗竭。随后，pDC浸润淋巴组织和黏膜组织，其循环群体在慢性感染中减少；IFN-I可能由其他细胞产生。来自非人类灵长类动物的数据表明，急性感染时迅速的IFN-I信号传导至关重要。虽然一些研究表明，在未联合抗逆转录病毒疗法（cART）的情况下给予IFN-I是有益的，但其他研究表明，在慢性抗逆转录病毒治疗抑制的HIV感染中刺激或阻断IFN-I信号传导已取得了积极成果。在此，我们描述了HIV和IFN-I的历史、IFN-I的来源、IFN-I对HIV控制和宿主防御的影响，以及最近在猴免疫缺陷病毒（SIV）和HIV感染中的干预研究。
