Regulated localization of transposable element RNA during influenza A virus infection.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-06-16 DOI:10.1038/s44319-025-00498-2

Marie Lork, Liam Childs, Gauthier Lieber, Florence Kwaschik, Renate König, Benjamin G Hale

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引用次数: 0

Abstract

Influenza A virus (IAV) infection triggers derepression of host transposable elements (TEs), which have the potential to form double-stranded (ds)RNAs and could enhance innate antiviral immunity. However, the contribution of TEs to stimulating such pathways during infection is unknown, and it remains unclear whether derepressed TEs actually form dsRNAs. Here, we perform strand-specific total RNA-Seq on nucleus-associated and cytosolic fractions from cells infected with wild-type IAV or an engineered IAV lacking NS1, a dsRNA-binding interferon-antagonist protein. Both infections globally increase levels of host TE RNAs with bioinformatic and experimental evidence for double-strandedness. However, NS1-deficient IAV leads to significantly more of these putative dsRNA-forming TEs accumulating in the cytosolic fraction. Co-precipitations identify that wild-type NS1, but not a dsRNA-binding mutant, associates with these TEs, and microscopy shows co-localization of wild-type NS1 with dsRNA in perinuclear regions. Our data reveal the double-stranded nature of some IAV-triggered host TEs and suggest that NS1-mediated sequestration could limit their engagement of cytosolic innate immune sensors.

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甲型流感病毒感染期间转座因子RNA的调控定位。

甲型流感病毒（IAV）感染触发宿主转座因子（TEs）的抑制，而te具有形成双链rna的潜力，可以增强先天抗病毒免疫。然而，在感染过程中，TEs对刺激这些通路的作用尚不清楚，并且尚不清楚被抑制的TEs是否真的形成了dsrna。在这里，我们对感染野生型IAV或缺乏NS1（一种dsrna结合干扰素拮抗剂蛋白）的工程IAV的细胞的核相关和细胞质部分进行了链特异性总rna测序。这两种感染在全球范围内都增加了宿主TE rna的水平，具有双链的生物信息学和实验证据。然而，缺乏ns1的IAV显著增加了这些假定的形成dsrna的TEs在细胞质部分的积累。共沉淀鉴定出野生型NS1，而非dsRNA结合突变体，与这些te相关，显微镜显示野生型NS1与dsRNA在核周区域共定位。我们的数据揭示了一些iav触发的宿主te的双链性质，并表明ns1介导的隔离可能限制它们与细胞质先天免疫传感器的结合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.