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oai:repisalud.isciii.es:20.500.12105/265812025-12-18T13:00:08Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Casadémont, Isabelle author Ayala-Suarez, Ruben author Modhiran, Naphak author Tawfik, Ahmed author Prot, Matthieu author Paul, Richard author Simon-Lorière, Etienne author Díez-Fuertes, Francisco author Ubol, Sukathida author Alcamí, José author Sakuntabhai, Anavaj author 2025-02-20 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. Casadémont I, Ayala-Suárez R, Modhiran N, Tawfik A, Prot M, Paul R, Simon-Lorière E, Díez-Fuertes F, Ubol S, Alcamí J, Sakuntabhai A. miRNome analysis reveals mir-155-5p as a protective factor to dengue infection in a resistant Thai cohort. Med Microbiol Immunol. 2025 Feb 20;214(1):13. 10.1007/s00430-025-00821-7 1432-1831 0300-8584 Medical microbiology and immunology 39976655 https://hdl.handle.net/20.500.12105/26581 Dengue RNA-Seq Resistance miR-155-5p miRNome microRNA miRNome analysis reveals mir-155-5p as a protective factor to dengue infection in a resistant Thai cohort