miRNome分析显示,mir-155-5p是泰国耐药人群中登革热感染的保护因子。

IF 5.5 3区 医学 Q1 IMMUNOLOGY
Isabelle Casadémont, Rubén Ayala-Suárez, Naphak Modhiran, Ahmed Tawfik, Matthieu Prot, Richard Paul, Etienne Simon-Lorière, Francisco Díez-Fuertes, Sukathida Ubol, José Alcamí, Anavaj Sakuntabhai
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引用次数: 0

摘要

登革热病毒(DENV)是一种全球健康威胁,每年约有3.9亿人感染,感染范围从轻度登革热到严重登革出血热和休克综合征。MicroRNA (miRNA)是重要的转录后调控因子,可能调控宿主对DENV感染的抗性。本研究旨在鉴定参与DENV感染自然抗性的mirna。根据登革热流行地区个体的抗denv抗体水平,将其分为易感(SD)和耐药(RD)两类。尽管当地登革热病毒感染率很高,但RD个体血清检测呈阴性。体外评估单核细胞对DENV感染的易感性。在模拟或DENV-2感染时,对每组7人的单核细胞的miRNome谱进行评估。在感染DENV-1、DENV-2、DENV-3和DENV-4血清型的HeLa细胞中,使用miRNA模拟物分析差异表达的miRNA的抗病毒作用。我们对miRNA模拟转染的细胞进行RNA-seq,以鉴定与DENV蛋白相互作用的miRNA靶向基因。来自RD个体的单核细胞在体外表现出较低的DENV-2产量。DENV-2感染后,RD组单核细胞中miR-155、miR-132-3p、miR-576-5p过表达。转染miR-155-5p模拟减少了HeLa细胞中的DENV感染和病毒产生,调节了18个与DENV蛋白相互作用的基因,并下调了参与干扰素反应、TP53调节、细胞凋亡和囊泡运输的靶基因(如HSD17B12、ANXA2)。因此,我们发现来自RD个体的单核细胞表现出不同的miRNA表达谱和减少的病毒产生。体外miR-155-5p上调诱导抗病毒状态,揭示治疗登革热的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
miRNome analysis reveals mir-155-5p as a protective factor to dengue infection in a resistant Thai cohort.

Dengue virus (DENV) is a global health threat, with approximately 390 million infections annually, ranging from mild dengue fever to severe dengue hemorrhagic fever and shock syndrome. MicroRNA (miRNA) are crucial post-transcriptional regulators which may regulate host resistance to DENV infection. This study aimed to identify miRNAs involved in natural resistance to DENV infection. Individuals from a dengue-endemic area were classified as susceptible (SD) or resistant (RD) according to their anti-DENV antibody status. RD individuals were seronegative despite high local DENV infection prevalence. Monocytes susceptibility to DENV infection was assessed in vitro. The miRNome profiles of the monocytes from 7 individuals per group were assessed upon mock or DENV-2 infection. The antiviral effect of differentially expressed miRNAs was analyzed using miRNA mimics in HeLa cells followed by infection with DENV-1, DENV-2, DENV-3, and DENV-4 serotypes. We performed RNA-seq on miRNA mimic-transfected cells to identify miRNA-targeted genes interacting with DENV proteins. Monocytes from RD individuals exhibit lower DENV-2 production in vitro. The miRNAs miR-155, miR-132-3p, miR-576-5p were overexpressed in monocytes from RD group upon DENV-2 infection. The transfection of miR-155-5p mimic reduced DENV infection and viral production in HeLa cells, regulating 18 genes interacting with DENV proteins and downregulating target genes involved in interferon response, TP53 regulation, apoptosis, and vesicle trafficking (e.g. HSD17B12, ANXA2). Therefore, we show that monocytes from RD individuals show a distinct miRNA expression profile and reduced viral production. In vitro miR-155-5p upregulation induces an antiviral state, revealing potential therapeutic targets to treat dengue.

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来源期刊
CiteScore
10.60
自引率
0.00%
发文量
29
审稿时长
1 months
期刊介绍: Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens. MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question. The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention. The following categories of manuscripts will not be considered for publication in MMIM: submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest, manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs, manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action, manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem, case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.
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