几种生物分子缩合物在哺乳动物细胞中组装以响应病毒感染。其中研究最多的是应激颗粒(SGs),已提出促进抗病毒先天免疫信号通路,包括RLR-MAVS,蛋白激酶R(PKR),和OAS-RNaseL途径。然而,最近的研究表明,SGs负调节或不影响抗病毒信号。相反,SG-成核蛋白,G3BP1可以通过将病毒RNA浓缩成病毒聚集的RNA缩合物来扰乱病毒RNA生物学,从而解释了为什么病毒经常拮抗G3BP1或劫持其RNA缩合功能。然而,最近发现的凝析油,称为双链RNA诱导的病灶,促进PKR和OAS-RNaseL抗病毒途径的激活。此外,在许多病毒感染期间已观察到称为RNaseL诱导体(RLB)的SG样缩合物。包括SARS-CoV-2和几种黄病毒。RLBs可能在促进细胞和病毒RNA的衰变中起作用,以及促进核糖体相关的信号通路。在这里,我们回顾了抗病毒生物分子缩合物领域的最新进展,我们提供了对抗病毒应答过程中规范SGs和G3BP1的作用的观点。
Several biomolecular condensates assemble in mammalian cells in response to viral infection. The most studied of these are stress granules (SGs), which have been proposed to promote antiviral innate immune signaling pathways, including the RLR-MAVS, the protein kinase R (PKR), and the OAS-RNase L pathways. However, recent studies have demonstrated that SGs either negatively regulate or do not impact antiviral signaling. Instead, the SG-nucleating protein, G3BP1, may function to perturb viral RNA biology by condensing viral RNA into viral-aggregated RNA condensates, thus explaining why viruses often antagonize G3BP1 or hijack its RNA condensing function. However, a recently identified
condensate, termed double-stranded RNA-induced foci, promotes the activation of the PKR and OAS-RNase L antiviral pathways. In addition, SG-like condensates known as an RNase L-induced bodies (RLBs) have been observed during many viral infections, including SARS-CoV-2 and several flaviviruses. RLBs may function in promoting decay of cellular and viral RNA, as well as promoting ribosome-associated signaling pathways. Herein, we review these recent advances in the field of antiviral biomolecular condensates, and we provide perspective on the role of canonical SGs and G3BP1 during the antiviral response.