Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago 8910060, Chile.
Centro de Investigación e Innovación Biomédica, Facultad de Medicina, Universidad de los Andes, Santiago 7620001, Chile.
Cells. 2021 Sep 9;10(9):2378. doi: 10.3390/cells10092378.
A key characteristic of Human immunodeficiency virus type 1 (HIV-1) infection is the generation of latent viral reservoirs, which have been associated with chronic immune activation and sustained inflammation. Macrophages play a protagonist role in this context since they are persistently infected while being a major effector of the innate immune response through the generation of type-I interferons (type I IFN) and IFN-stimulated genes (ISGs). The balance in the IFN signaling and the ISG induction is critical to promote a successful HIV-1 infection. Classically, the IFNs response is fine-tuned by opposing promotive and suppressive signals. In this context, it was described that HIV-1-infected macrophages can also synthesize some antiviral effector ISGs and, positive and negative regulators of the IFN/ISG signaling. Recently, epitranscriptomic regulatory mechanisms were described, being the N6-methylation (m6A) modification on mRNAs one of the most relevant. The epitranscriptomic regulation can affect not only IFN/ISG signaling, but also type I IFN expression, and viral fitness through modifications to HIV-1 RNA. Thus, the establishment of replication-competent latent HIV-1 infected macrophages may be due to non-classical mechanisms of type I IFN that modulate the activation of the IFN/ISG signaling network.
人类免疫缺陷病毒 1 型（HIV-1）感染的一个关键特征是产生潜伏的病毒库，这与慢性免疫激活和持续炎症有关。巨噬细胞在这种情况下起着重要作用，因为它们在持续感染的同时，通过产生 I 型干扰素（type I IFN）和干扰素刺激基因（ISGs），成为先天免疫反应的主要效应器。IFN 信号和 ISG 诱导之间的平衡对于促进 HIV-1 感染的成功至关重要。传统上，IFNs 反应通过相反的促进和抑制信号进行微调。在这种情况下，已经描述了 HIV-1 感染的巨噬细胞也可以合成一些抗病毒效应 ISGs，以及 IFN/ISG 信号的正调节因子和负调节因子。最近，描述了转录后调控机制，其中 mRNA 的 N6-甲基化（m6A）修饰是最相关的一种。转录后调控不仅可以影响 IFN/ISG 信号，还可以通过修饰 HIV-1 RNA 影响 I 型 IFN 的表达和病毒适应性。因此，复制型潜伏 HIV-1 感染巨噬细胞的建立可能归因于调节 IFN/ISG 信号网络激活的非经典 I 型 IFN 机制。
