A virus-derived microRNA targets immune response genes during SARS-CoV-2 infection.
A virus-derived microRNA targets immune response genes during SARS-CoV-2 infection.
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DOI：
10.15252/embr.202154341
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发表时间：
2022-02-03
期刊：
影响因子：
7.7
通讯作者：
Cecere G
中科院分区：
文献类型：
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作者：
Singh M;Chazal M;Quarato P;Bourdon L;Malabat C;Vallet T;Vignuzzi M;van der Werf S;Behillil S;Donati F;Sauvonnet N;Nigro G;Bourgine M;Jouvenet N;Cecere G
SARS-CoV-2感染导致严重COVID-19患者的干扰素反应受损。然而，SARS-CoV-2如何干扰宿主免疫反应尚不完全清楚。在这里，我们对来自SARS-CoV-2感染的人类细胞的小RNA进行测序，并鉴定出来自病毒基因组最近进化区域的microRNA（miRNA）。我们发现，病毒衍生的miRNA在感染细胞中通过酶Dicer产生两种miRNA亚型，它们被加载到Argonaute蛋白中。此外，主要的miRNA亚型靶向干扰素刺激基因的3′UTR，并以miRNA样方式抑制其表达。最后，在COVID-19患者的鼻咽拭子中检测到两种病毒miRNA亚型。我们认为SARS-CoV-2可能利用病毒衍生的miRNA来劫持宿主的miRNA机制，这可能有助于逃避干扰素介导的免疫反应。SARS-CoV-2以Dicer依赖的方式产生两种来自ORF-7a转录物的保守茎环结构的miRNA。这些病毒衍生的miRNAs与宿主Argonaute相互作用，可以抑制培养细胞中的宿主先天免疫应答基因。
SARS‐CoV‐2 infection results in impaired interferon response in patients with severe COVID‐19. However, how SARS‐CoV‐2 interferes with host immune responses is incompletely understood. Here, we sequence small RNAs from SARS‐CoV‐2‐infected human cells and identify a microRNA (miRNA) derived from a recently evolved region of the viral genome. We show that the virus‐derived miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer, which are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3′UTR of interferon‐stimulated genes and represses their expression in a miRNA‐like fashion. Finally, the two viral miRNA isoforms were detected in nasopharyngeal swabs from COVID‐19 patients. We propose that SARS‐CoV‐2 can potentially employ a virus‐derived miRNA to hijack the host miRNA machinery, which could help to evade the interferon‐mediated immune response. SARS‐CoV‐2 produces two miRNAs derived from a conserved stem‐loop structure of the ORF‐7a transcript in a Dicer‐dependent manner. These virus‐derived miRNAs interact with host Argonaute and can repress host innate immune response genes in cultured cells.