{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307959/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307959"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Membrane Fusion Inhibition, Immune Modulation, and Cholesterol Synthesis Dysregulation During Dengue Virus Inhibition by 25-Hydroxycholesterol","description":"Physicochemical properties and composition of cellular membranes are crucial for regulating broad cellular responses including signaling and defense against pathogens. Dengue virus (DENV) exploits cholesterol-rich membranes and host lipid pathways, such as cholesterol biosynthesis, lipid raft organization, and lipid droplet formation, for entry, replication, and assembly. Additionally, lipid-based plasma membrane signaling can trigger innate immune responses that attenuate viral growth, underscoring the dual role of lipids in facilitating and restricting DENV infection. Here, we demonstrate that 25-hydroxycholesterol (25-HC), an oxidized cholesterol metabolite, inhibits DENV infection through a multifaceted mechanism. 25-HC disrupts viral membrane fusion by altering cholesterol distribution and lipid raft organization, impairing the binding and fusion of the DENV envelope (E) protein with host membranes. Additionally, 25-HC modulates host cholesterol metabolism by suppressing biosynthesis pathways essential for viral replication while enhancing lipid droplet formation and stress-response pathways. Transcriptomic analyses reveal that 25-HC primes innate immune responses, activating pro-inflammatory pathways such as the NLRP3 inflammasome and MAPK signaling, while selectively modulating interferon-stimulated gene expression. Notably, 25-HC exhibits synergistic antiviral effects when combined with direct-acting antivirals like Remdesivir, underscoring its potential in combination therapies. These findings establish 25-HC as a promising candidate for host-directed antiviral strategies against DENV and other enveloped viruses.","dates":{"publication":"2026/04/07"},"accession":"GSE307959","cross_references":{"GSM":["GSM9234651","GSM9234650","GSM9234649","GSM9234646","GSM9234645","GSM9234648","GSM9234647","GSM9234652"],"GPL":["34290"],"GSE":["307959"],"taxon":["Mus musculus"]}}