{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:28:53Z","timestamp":1781886533905,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centro de Investigaci\u00f3n y Estudios Avanzados IPN"},{"name":"L.C.-B."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Dengue Virus (DENV) induces assembly of the NOD-like receptor (NLR) family pyrin domain containing-3 (NLRP3) inflammasome and autophagy, which are closely interconnected processes playing crucial roles in lipid metabolism and DENV replication. However, the autophagy\u2013NLRP3 activation interplay during DENV infection in human endothelial cells remains incompletely understood. We aimed to elucidate effects of NLRP3 activation on autophagy during DENV-2 infection. We investigated how autophagy-related molecules are altered by NLRP3 inhibition and how this regulation affects lipid metabolism, through the master lipid transcription factors SREBP-1 and 2, which increase the expression of their target lipid-synthesizing genes such as fatty acid synthase (FAS) in a model of microvascular endothelial cells (HMEC-1). We demonstrated a dynamic interplay between inflammasome activity and autophagy in DENV-infected HMEC-1 cells: autophagy increases early during infection and decreases as inflammasome activity increases. NLRP3 inflammasome inhibition affects viral replication. Glyburide (an inflammasome inhibitor) treatment partially inhibited DENV-induced NLRP3 inflammasome activation. Non-structural viral protein expression (NS3 and NS5) and infectious viral-particle formation were significantly reduced. NLRP3 inhibition also downregulated SREBP-1 and SREBP-2 activation. These findings provide new insights into the modulation of the interconnected NLRP3 inflammasome, autophagy, and lipid metabolism pathways, presenting a promising therapeutic strategy for severe clinical forms of dengue.<\/jats:p>","DOI":"10.3390\/pathogens14121292","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:47:26Z","timestamp":1765889246000},"page":"1292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Interplay Between NLRP3 Activation by DENV-2 and Autophagy and Its Impact on Lipid Metabolism in HMEC-1 Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9658-2727","authenticated-orcid":false,"given":"Giovani","family":"Visoso-Carvajal","sequence":"first","affiliation":[{"name":"Departamento de Biomedicina Molecular, Centro de Investigaci\u00f3n y Estudios Avanzados (Cinvestav-IPN) Av. IPN # 2508 Col. 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