{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T12:34:58Z","timestamp":1776515698085,"version":"3.51.2"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"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. Genet."],"abstract":"<jats:p>A previous study investigated a genomic region on chromosome 1 associated with reduced human immunodeficiency virus type 1 (HIV) set-point viral load, implicating <jats:italic>CHD1L<\/jats:italic> as a novel HIV inhibitory factor. However, given that regulatory variants can influence expression of multiple nearby genes, further work is necessary to determine the impact of genetic variants on other genes in the region. This study evaluates the potential for genetic regulation of <jats:italic>PRKAB2<\/jats:italic>, a gene located upstream of <jats:italic>CHD1L<\/jats:italic> and encoding the \u03b22 regulatory subunit of the AMPK complex, and for downstream impacts on HIV pathogenesis. Using genotype and gene expression data from the Gene Expression Omnibus repository and Genotype-Tissue Expression database, we observed cell-type-specific correlations between <jats:italic>CHD1L<\/jats:italic> and <jats:italic>PRKAB2<\/jats:italic> expression, with a strong positive association in whole blood and negative correlation in monocytes. Notably, we found that individuals with HIV set-point viral load associated variants exhibited significantly reduced <jats:italic>PRKAB2<\/jats:italic> expression in imputed whole blood models and <jats:italic>ex vivo<\/jats:italic> monocytes. Functional analyses using <jats:italic>PRKAB2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> induced pluripotent stem cells suggest that <jats:italic>PRKAB2<\/jats:italic> loss-of-function may influence <jats:italic>CHD1L<\/jats:italic> expression, and genes regulating cytokine activity, growth factor signaling, and pluripotency pathways associated with HIV infection. These results suggest that gene expression changes driven by HIV set-point viral load associated variants in the chromosome 1 impact multiple genes and, by influencing expression of <jats:italic>PRKAB2<\/jats:italic>, may result in altered expression of critical immune signaling processes. These findings advance our understanding of the contribution of host genetics on HIV pathogenesis and identifies new targets for <jats:italic>ex vivo<\/jats:italic> functional studies.<\/jats:p>","DOI":"10.3389\/fgene.2025.1551171","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T06:53:35Z","timestamp":1741244015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Chromosome 1 variants associated with decreased HIV set-point viral load correlate with PRKAB2 expression changes"],"prefix":"10.3389","volume":"16","author":[{"given":"Riley H.","family":"Tough","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"McLaren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.3390\/cells10051118","article-title":"Multifaceted role of AMPK in viral infections","volume":"10","author":"Bhutta","year":"2021","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1126\/science.1152725","article-title":"Identification of host proteins required for HIV infection through a functional genomic screen","volume":"319","author":"Brass","year":"2008","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"190221","DOI":"10.1098\/rsob.190221","article-title":"A practical view of fine-mapping and gene prioritization in the post-genome-wide association era","volume":"10","author":"Broekema","year":"2020","journal-title":"Open Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.1007\/s00018-010-0454-z","article-title":"AMP-activated protein kinase and its downstream transcriptional pathways","volume":"67","author":"Cant\u00f3","year":"2010","journal-title":"Cell. 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