Viral hijacking of hnRNPH1 unveils a G-quadruplex-driven mechanism of stress control

IF 20.6 1区 医学 Q1 MICROBIOLOGY Cell host & microbe Pub Date : 2024-08-01 DOI:10.1016/j.chom.2024.07.006
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Abstract

Viral genomes are enriched with G-quadruplexes (G4s), non-canonical structures formed in DNA or RNA upon assembly of four guanine stretches into stacked quartets. Because of their critical roles, G4s are potential antiviral targets, yet their function remains largely unknown. Here, we characterize the formation and functions of a conserved G4 within the polymerase coding region of orthoflaviviruses of the Flaviviridae family. Using yellow fever virus, we determine that this G4 promotes viral replication and suppresses host stress responses via interactions with hnRNPH1, a host nuclear protein involved in RNA processing. G4 binding to hnRNPH1 causes its cytoplasmic retention with subsequent impacts on G4-containing tRNA fragments (tiRNAs) involved in stress-mediated reductions in translation. As a result, these host stress responses and associated antiviral effects are impaired. These data reveal that the interplay between hnRNPH1 and both host and viral G4 targets controls the integrated stress response and viral replication.

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病毒对 hnRNPH1 的劫持揭示了一种由 G 型四联体驱动的应激控制机制
病毒基因组中富含 G-四联体(G4s),这是 DNA 或 RNA 中四个鸟嘌呤链段组装成叠加四联体后形成的非经典结构。由于其关键作用,G4s 是潜在的抗病毒靶标,但其功能在很大程度上仍不为人所知。在这里,我们描述了黄热病病毒科正黄热病病毒聚合酶编码区中保守的 G4 的形成和功能。利用黄热病病毒,我们确定这种 G4 通过与参与 RNA 处理的宿主核蛋白 hnRNPH1 相互作用,促进病毒复制并抑制宿主的应激反应。G4 与 hnRNPH1 结合会导致其在细胞质中滞留,进而影响含 G4 的 tRNA 片段(tiRNA),这些片段参与了应激介导的翻译减少。因此,这些宿主应激反应和相关的抗病毒效应受到了损害。这些数据揭示了 hnRNPH1 与宿主和病毒 G4 靶点之间的相互作用控制着综合应激反应和病毒复制。
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来源期刊
Cell host & microbe
Cell host & microbe 生物-微生物学
CiteScore
45.10
自引率
1.70%
发文量
201
审稿时长
4-8 weeks
期刊介绍: Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.
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