{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T22:53:11Z","timestamp":1772491991545,"version":"3.50.1"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The advent of effective combination antiretroviral therapy (cART) has significantly improved HIV-1 treatment, saving millions of lives. However, HAND remains a concern, particularly among aging individuals with HIV-1. The mechanisms underlying HAND are not well understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study investigated the role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and its upstream regulator, signal transducer, and activator of transcription 1 (STAT1), in HAND pathology. Using the SH-SY5Y neuroblastoma cell line and HIV-infected humanized mice, we examined the effects of the cART drugs, HIV Tat protein, and HIV-1 virus on STAT1 and IFIT3 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that HIV-1 exposure significantly upregulated STAT1 and IFIT3, contributing to neuroinflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study identified IFIT3 as a critical molecular marker for HAND, suggesting its potential as a therapeutic target and offering new insights into disease pathology and treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1532318","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:14:11Z","timestamp":1756268051000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["IFIT3 activation significantly contributes to 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