{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T22:12:47Z","timestamp":1784585567299,"version":"3.55.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"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>Acquired Immune Deficiency Syndrome (AIDS) is a chronic and life-threatening condition caused by the human immunodeficiency virus (HIV), which severely weakens the immune system. Despite advances in treatment, AIDS remains incurable. Understanding the molecular mechanisms underlying AIDS progression is crucial for developing effective therapeutic strategies. Therefore, this study aims to identify hub genes associated with AIDS susceptibility and progression, as well as to elucidate potential molecular mechanisms involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used the Gene Expression Omnibus (GEO) dataset GSE76246 for this study. Differentially expressed genes (DEGs) were screened, and Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct gene modules associated with HIV infection. Hub genes were identified using the CytoHubba plugin, and their expression profiles were assessed using box plots. The diagnostic potential of these genes was evaluated using receiver operating characteristic (ROC) analysis. Functional enrichment and Gene Set Enrichment Analysis (GSEA) were conducted to identify key biological pathways. Additionally, we analyzed immune cell infiltration and constructed drug-gene interaction, miRNA and transcription factor (TF) regulatory networks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>101 intersection genes were identified by combining DEGs, Oxidative stress genes and module genes from WGCNA. Functional enrichment analysis highlighted key pathways, including oxidative stress response and apoptotic signaling. A protein-protein interaction (PPI) network analysis identified 10 hub genes (TP53, AKT1, JUN, CTNNB1, PXDN, MAPK3, FOS, MMP9, FOXO1, STAT1), which showed strong diagnostic potential, as evidenced by ROC curve analysis. Immune infiltration analysis revealed significant associations between hub genes and various immune cell populations. Furthermore, drug-gene interaction analysis predicted several potential therapeutic compounds. Additionally, miRNA and TF regulatory networks were constructed, identifying critical regulatory elements influencing the expression of hub genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identified ten hub genes (TP53, AKT1, JUN, CTNNB1, PXDN, MAPK3, FOS, MMP9, FOXO1, STAT1) that play crucial roles in HIV infection and progression. These genes serve as potential biomarkers for HIV diagnosis and therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1600713","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T04:11:14Z","timestamp":1749701474000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrated bioinformatics analysis identifies hub genes and immune regulatory networks in HIV infection"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaoxia","family":"Pang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huatuo","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"B1","unstructured":"UNAIDS financial estimates\n          \n          \n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4449","article-title":"Hiv and the spectrum of human disease","volume":"235","author":"Lucas","year":"2015","journal-title":"J Pathol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv218","article-title":"Precise quantitation of the latent hiv-1 reservoir: implications for eradication strategies","volume":"212","author":"Crooks","year":"2015","journal-title":"J Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2022.199034","article-title":"Identification of 5\u2019 Upstream sequence involved in hspbp1 gene transcription and its downregulation during hiv-1 infection","volume":"324","author":"Iyer","year":"2023","journal-title":"Virus Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.827717","article-title":"Counterakting hiv: toward a \u201cBlock and clear\u201d Strategy","volume":"12","author":"Pasquereau","year":"2022","journal-title":"Front Cell infection Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/jmp.12613","article-title":"The role of latency reversal in hiv cure strategies","volume":"51","author":"Tanaka","year":"2022","journal-title":"J Med primatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.10.026","article-title":"Transcriptome analysis of primary monocytes shows global down-regulation of genetic networks in hiv viremic patients versus long-term non-progressors","volume":"435","author":"Wu","year":"2013","journal-title":"Virology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e30900","article-title":"Expression pattern analysis of the long non-coding rnas (Tincr, rp11-573d15.8, rp11-156e8.1), and their target genes (Akt1, foxo1 and mapk3) in patients with hiv infection, and elite controllers","volume":"10","author":"Sadri Nahand","year":"2024","journal-title":"Heliyon"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-1792-1_28","article-title":"Effects of exercise on the immune function, quality of life, and mental health in hiv\/aids individuals","volume":"1228","author":"Dianatinasab","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00423","article-title":"Visualizing the immune system: providing key insights into hiv\/siv infections","volume":"9","author":"Estes","year":"2018","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7493-1_12","article-title":"Profiling tumor infiltrating immune cells with cibersort","volume":"1711","author":"Chen","year":"2018","journal-title":"Methods Mol Biol (Clifton NJ)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1089\/aid.2016.0273","article-title":"Hiv-1 infection primes macrophages through stat signaling to promote enhanced inflammation and viral replication","volume":"33","author":"Appelberg","year":"2017","journal-title":"AIDS Res Hum Retroviruses"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01057-20","article-title":"Nf-\u03bab-interacting long noncoding rna regulates hiv-1 replication and latency by repressing nf-\u03bab signaling","volume":"94","author":"Wang","year":"2020","journal-title":"J Virol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12985-018-0959-x","article-title":"Inhibition of hiv early replication by the P53 and its downstream gene P21","volume":"15","author":"Shi","year":"2018","journal-title":"Virol J"},{"key":"B15","doi-asserted-by":"publisher","first-page":"66","DOI":"10.21037\/atm-22-6450","article-title":"Prediction and analysis of osteoarthritis hub genes with bioinformatics","volume":"11","author":"Zhong","year":"2023","journal-title":"Ann Trans Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12879-023-08883-9","article-title":"Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis","volume":"24","author":"Liang","year":"2024","journal-title":"BMC Infect Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1434105","article-title":"A combination analysis based on bioinformatics tools reveals new signature genes related to maternal obesity and fetal programming","volume":"11","author":"Liu","year":"2024","journal-title":"Front Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw937","article-title":"The string database in 2017: quality-controlled protein-protein association networks, made broadly accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0742-9","article-title":"Foxo1 promotes hiv latency by suppressing er stress in T cells","volume":"5","author":"Vallejo-Gracia","year":"2020","journal-title":"Nat Microbiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/v11030200","article-title":"Immune activation, inflammation, and non-aids co-morbidities in hiv-infected patients under long-term art","volume":"11","author":"Zicari","year":"2019","journal-title":"Viruses"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221256498","article-title":"Hiv-1 nef impairs mhc class ii antigen presentation and surface expression","volume":"98","author":"Stumptner-Cuvelette","year":"2001","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/cells12030512","article-title":"The role of tp53 in adaptation and evolution","volume":"12","author":"Voskarides","year":"2023","journal-title":"Cells"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0306189","article-title":"Inhibition of hiv-1 replication by rna interference of P53 expression","volume":"80","author":"Pauls","year":"2006","journal-title":"J leukocyte Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008076107","article-title":"Hiv-1 viral infectivity factor interacts with tp53 to induce G2 cell cycle arrest and positively regulate viral replication","volume":"107","author":"Izumi","year":"2010","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B25","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s12985-016-0595-2","article-title":"Highly activated P53 contributes to selectively increased apoptosis of latently hiv-1 infected cells upon treatment of anticancer drugs","volume":"13","author":"Shin","year":"2016","journal-title":"Virol J"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089489","article-title":"Evidence for an epistatic effect between tp53 R72p and mdm2 T309g snps in hiv infection: A cross-sectional study in women from south Brazil","volume":"9","author":"Hartwig","year":"2014","journal-title":"PloS One"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/cimb44100334","article-title":"Expression of akt1 related with clinicopathological parameters in clear cell renal cell carcinoma","volume":"44","author":"Choi","year":"2022","journal-title":"Curr Issues Mol Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s13402-022-00744-y","article-title":"Pkmyt1 inhibits lung adenocarcinoma progression by abrogating akt1 activity","volume":"46","author":"Wang","year":"2023","journal-title":"Cell Oncol (Dordrecht Netherlands)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1080\/15513815.2024.2393357","article-title":"Akt1 and mapk8: new targets for gestational diabetes mellitus","volume":"43","author":"Turkyilmaz","year":"2024","journal-title":"Fetal Pediatr Pathol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030146","article-title":"Hmba releases P-tefb from hexim1 and 7sk snrna via pi3k\/akt and activates hiv transcription","volume":"3","author":"Contreras","year":"2007","journal-title":"PloS Pathog"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.11.033","article-title":"Ezh2 phosphorylation regulates tat-induced hiv-1 transactivation via ros\/akt signaling pathway","volume":"589","author":"Zhang","year":"2015","journal-title":"FEBS Lett"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.4.2304","article-title":"Trail-mediated apoptosis in hiv-1-infected macrophages is dependent on the inhibition of akt-1 phosphorylation","volume":"177","author":"Huang","year":"2006","journal-title":"J Immunol (Baltimore Md: 1950)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01764-23","article-title":"C-jun signaling during initial hsv-1 infection modulates latency to enhance later reactivation in addition to directly promoting the progression to full reactivation","volume":"98","author":"Dochnal","year":"2024","journal-title":"J Virol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13792","article-title":"Transcriptional activation of jun and fos members of the ap-1 complex is a conserved signature of immune aging that contributes to inflammaging","volume":"22","author":"Karakaslar","year":"2023","journal-title":"Aging Cell"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00765-4","article-title":"The ap-1 transcription factors C-jun and junb are essential for cd8\u03b1 Conventional dendritic cell identity","volume":"28","author":"Novoszel","year":"2021","journal-title":"Cell Death differentiation"},{"key":"B36","doi-asserted-by":"publisher","first-page":"53","DOI":"10.12717\/dr.2020.24.1.53","article-title":"Xrp44x enhances the cytotoxic activity of natural killer cells by activating the C-jun N-terminal kinase signaling pathway","volume":"24","author":"Kim","year":"2020","journal-title":"Dev Reprod"},{"key":"B37","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13287-022-02735-0","article-title":"Osteogenic differentiation of mesenchymal stem cells promotes C-jun-dependent secretion of interleukin 8 and mediates the migration and differentiation of cd4(+) T cells","volume":"13","author":"Ye","year":"2022","journal-title":"Stem Cell Res Ther"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.39.27981","article-title":"Erk map kinase links cytokine signals to activation of latent hiv-1 infection by stimulating a cooperative interaction of ap-1 and nf-kappab","volume":"274","author":"Yang","year":"1999","journal-title":"J Biol Chem"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108015","article-title":"Ap-1\/C-fos supports siv and hiv-1 latency in cd4 T cells infected","volume":"26","author":"Cobos Jim\u00e9nez","year":"2023","journal-title":"In vivo iScience"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2005.12.007","article-title":"Balancing cell adhesion and wnt signaling, the key role of beta-catenin","volume":"16","author":"Brembeck","year":"2006","journal-title":"Curr Opin Genet Dev"},{"key":"B41","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13027-020-00297-5","article-title":"Investigation of ctnnb1 gene mutations and expression in hepatocellular carcinoma and cirrhosis in association with hepatitis B virus infection","volume":"15","author":"Javanmard","year":"2020","journal-title":"Infect Agents Cancer"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/biom10091256","article-title":"Impact of conventional and atypical mapks on the development of metabolic diseases","volume":"10","author":"Kassouf","year":"2020","journal-title":"Biomolecules"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1097\/qai.0000000000003125","article-title":"Hiv increases the risk of cigarette smoke-induced emphysema through mmp-9","volume":"92","author":"Staitieh","year":"2023","journal-title":"J acquired Immune deficiency syndromes (1999)"},{"key":"B44","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3858\/emm.2009.41.2.011","article-title":"Extracellular hiv-1 tat up-regulates expression of matrix metalloproteinase-9 via a mapk-nf-kappab dependent pathway in human astrocytes","volume":"41","author":"Ju","year":"2009","journal-title":"Exp Mol Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jctube.2022.100308","article-title":"Neutrophils and lymphocytes in relation to mmp-8 and mmp-9 levels in pulmonary tuberculosis and hiv co-infection","volume":"27","author":"Alisjahbana","year":"2022","journal-title":"J Clin tuberculosis other mycobacterial Dis"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-013-0197-3","article-title":"Matrix metalloproteinase levels in early hiv infection and relation to in vivo brain status","volume":"19","author":"Li","year":"2013","journal-title":"J neurovirol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12647","article-title":"Association between smoking status assessed with plasma-cotinine and inflammatory and endothelial biomarkers in hiv-positive and hiv-negative individuals","volume":"19","author":"Ahlstr\u00f6m","year":"2018","journal-title":"HIV Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0215825","article-title":"Impact of hiv-1 infection on the igf-1 axis and angiogenic factors in pregnant Cameroonian women receiving antiretroviral therapy","volume":"14","author":"Esemu","year":"2019","journal-title":"PloS One"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3851\/imp1867","article-title":"Ribavirin and interferon alter mmp-9 abundance in vitro and in hiv-hcv-coinfected patients","volume":"16","author":"Kennedy","year":"2011","journal-title":"Antiviral Ther"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007669","article-title":"Foxo1 transcription factor plays a key role in T cell-hiv-1 interaction","volume":"15","author":"Roux","year":"2019","journal-title":"PloS Pathog"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.2174\/1570162x19666210118151249","article-title":"Resveratrol promotes hiv-1 tat accumulation via akt\/foxo1 signaling axis and potentiates vorinostat to antagonize hiv-1 latency","volume":"19","author":"Feng","year":"2021","journal-title":"Curr HIV Res"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn9181","article-title":"Lncrna-gm targets foxo1 to promote T cell-mediated autoimmunity","volume":"8","author":"Chen","year":"2022","journal-title":"Sci Adv"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.771279","article-title":"Hsa-mir-31 governs T-cell homeostasis in hiv protection via ifn-\u0393-stat1-T-bet axis","volume":"12","author":"Zhu","year":"2021","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003976","article-title":"Chronic exposure to type-I ifn under lymphopenic conditions alters cd4 T cell homeostasis","volume":"10","author":"Le Saout","year":"2014","journal-title":"PloS Pathog"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22458","article-title":"Cross-talk between stat1 and pi3k\/akt signaling in hiv-1-induced blood-brain barrier dysfunction: role of ccr5 and implications for viral neuropathogenesis","volume":"88","author":"Yang","year":"2010","journal-title":"J Neurosci Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.10.023","article-title":"Mir-34a is involved in tat-induced hiv-1 long terminal repeat (Ltr) transactivation through the sirt1\/nf\u03bab pathway","volume":"586","author":"Zhang","year":"2012","journal-title":"FEBS Lett"},{"key":"B57","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1042\/BJ20150700","article-title":"The mirna mir-34a enhances hiv-1 replication by targeting pnuts\/ppp1r10, which negatively regulates hiv-1 transcriptional complex formation","volume":"470","author":"Kapoor","year":"2015","journal-title":"Biochem J"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1600713\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T04:11:16Z","timestamp":1749701476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1600713\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":57,"alternative-id":["10.3389\/fimmu.2025.1600713"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1600713","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,12]]},"article-number":"1600713"}}