{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:03:18Z","timestamp":1789113798557,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>HIV-1 mediated neurotoxicity is thought to be associated with HIV-1 viral proteins activating astrocytes and microglia by inducing inflammatory cytokines leading to the development of HIV-associated neurocognitive disorder (HAND). In the current study, we observe how HIV-1 Nef upregulates the levels of IL-6, IP-10, and TNF-\u03b1 around 6.0fold in normal human astrocytes (NHAs) compared to cell and empty vector controls. Moderate downregulation in the expression profile of inflammatory cytokines was observed due to RNA interference. Furthermore, we determine the impact of inflammatory cytokines in the upregulation of kynurenine pathway metabolites, such as indoleamine 2,3-dioxygenase (IDO), and 3-hydroxyanthranilic acid oxygenase (HAAO) in NHA, and found the same to be 3.0- and 3.2-fold, respectively. Additionally, the variation in the level of nitric oxide before and after RNA interference was significant. The upregulated cytokines and pathway-specific metabolites could be linked with the neurotoxic potential of HIV-1 Nef. Thus, the downregulation in cytokines and kynurenine metabolites observed after siRNA-Nef interference indicates the possibility of combining the RNA interference approach with current antiretroviral therapy to prevent neurotoxicity development.<\/jats:p>","DOI":"10.3390\/cells11203256","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T05:08:02Z","timestamp":1665983282000},"page":"3256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The NeuroinflammatoryPotential of HIV-1 NefVariants in Modulating the Gene Expression Profile of Astrocytes"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-7017","authenticated-orcid":false,"given":"Sushama","family":"Jadhav","sequence":"first","affiliation":[{"name":"Indian Council of Medical Research, Department of Molecular Biology, National AIDS Research Institute, 73, G Block, MIDC, Bhosari, P.O. Box No. 1895, Pune 411026, Maharashtra, India"},{"name":"Faculty of Health Sciences, Symbiosis International (Deemed University), Lavale, Mulshi, Pune 412115, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prajakta","family":"Makar","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Biotechnology (IBB), S. Phule Pune University, Pune 411007, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6420-9397","authenticated-orcid":false,"given":"Vijay","family":"Nema","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research, Department of Molecular Biology, National AIDS Research Institute, 73, G Block, MIDC, Bhosari, P.O. Box No. 1895, Pune 411026, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","unstructured":"(2022, July 28). Updated Information about HIV Prevalence Was Accessed in April 2022. Available online: https:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/JC3032_AIDS_Data_book_2021_En.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1089\/aid.2011.0172","article-title":"Functional Analysis of HIV Type 1 Nef Gene Variants from Adolescent and Adult Survivors of Perinatal Infection","volume":"28","author":"Zuo","year":"2012","journal-title":"AIDS Res. Hum. 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