{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:01:52Z","timestamp":1791943312336,"version":"4.3.4"},"reference-count":110,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2013NextGenerationEU","award":["760252\/28.12.2023"],"award-info":[{"award-number":["760252\/28.12.2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>p17, the human immunodeficiency virus type 1 (HIV-1) matrix protein traditionally associated with viral assembly, has been recently investigated for its extracellular functions linked to vascular damage. This review examines the molecular and pathogenic signatures by which p17 and its variants (vp17s) contribute to endothelial activation, aberrant angiogenesis, and vascular inflammation, highlighting their relevance even under effective antiretroviral therapy (ART). Specifically, p17 exerts chemokine-like activities by binding to chemokine (C-X-C motif) receptor-1 and 2 (CXCR-1\/2) on endothelial cells (ECs). This interaction triggers key signaling cascades, including the protein kinase B (Akt)-dependent extracellular signal-regulated kinase (ERK) pathway and endothelin-1\/endothelin receptor B axis, driving EC motility, capillary formation, and lymphangiogenesis. Variants such as S75X demonstrate enhanced lymphangiogenic potency, associating them with tumorigenic processes involved in non-Hodgkin lymphoma (NHL) pathogenesis. Importantly, p17 promotes endothelial von Willebrand factor (vWF) storage and secretion, implicating a pro-coagulant state that may trigger the increased thromboembolic risks observed in HIV-positive patients. Furthermore, p17 crosses the blood\u2013brain barrier (BBB) via CXCR-2-mediated pathways, contributing to neuroinflammation by activating microglia and astrocytes and amplifying monocyte chemoattractant protein-1 (MCP-1) levels, therefore playing a critical role in the development of HIV-associated neurocognitive disorders. Hence, the elaboration of potential therapeutic strategies finalized at inhibiting p17\/vp17s\u2019 interaction with their receptors could complement ART by addressing HIV-related neurovascular morbidity.<\/jats:p>","DOI":"10.3390\/ijms262411949","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T14:30:17Z","timestamp":1765463417000},"page":"11949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond Viral Assembly: The Emerging Role of HIV-1 p17 in Vascular Inflammation and Endothelial Dysfunction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3833-0184","authenticated-orcid":false,"given":"Ylenia","family":"Pastorello","sequence":"first","affiliation":[{"name":"Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8150-156X","authenticated-orcid":false,"given":"Nicoleta","family":"Arnaut","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Biochemistry, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"},{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Straist\u0103","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-9033","authenticated-orcid":false,"given":"Francesca","family":"Caccuri","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"},{"name":"Center for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Caruso","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"},{"name":"Center for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3767-4861","authenticated-orcid":false,"given":"Mark","family":"Slevin","sequence":"additional","affiliation":[{"name":"Center for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u015f, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1093\/infdis\/jiad327","article-title":"Geographic and Population Distributions of Human Immunodeficiency Virus (HIV)-1 and HIV-2 Circulating Subtypes: A Systematic Literature Review and Meta-Analysis (2010\u20132021)","volume":"228","author":"Williams","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10209","DOI":"10.1128\/JVI.00872-07","article-title":"Human Immunodeficiency Virus Type 1 Subtype Distribution in the Worldwide Epidemic: Pathogenetic and Therapeutic Implications","volume":"81","author":"Buonaguro","year":"2007","journal-title":"J. Virol."},{"key":"ref_3","first-page":"407","article-title":"HIV and Cardiovascular Disease: From Insights to Interventions","volume":"29","author":"Feinstein","year":"2021","journal-title":"Top. Antivir. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1161\/CIRCULATIONAHA.122.057443","article-title":"Cardiovascular Disease Among Persons Living With HIV: New Insights Into Pathogenesis and Clinical Manifestations in a Global Context","volume":"147","author":"Ntsekhe","year":"2023","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"\u0218oldea, S., Iov\u0103nescu, M., Berceanu, M., Mirea, O., Raicea, V., Bezn\u0103, M.C., Roc\u0219oreanu, A., and Donoiu, I. (2025). Cardiovascular Disease in HIV Patients: A Comprehensive Review of Current Knowledge and Clinical Implications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26051837"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1161\/CIRCRESAHA.124.323948","article-title":"Cardiac and Renal Comorbidities in Aging People Living With HIV","volume":"134","author":"McCutcheon","year":"2024","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"04078","DOI":"10.7189\/jogh.14.04078","article-title":"Higher Cardiovascular Disease Risks in People Living with HIV: A Systematic Review and Meta-Analysis","volume":"14","author":"Zhu","year":"2024","journal-title":"J. Glob. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1001\/jamacardio.2022.4873","article-title":"Performance of Cardiovascular Risk Prediction Models Among People Living With HIV: A Systematic Review and Meta-Analysis","volume":"8","author":"Soares","year":"2023","journal-title":"JAMA Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Arbune, M., Plesea-Condratovici, A., Arbune, A.-A., Andronache, G., Plesea-Condratovici, C., and Gutu, C. (2025). Cardiovascular Risk in People Living with HIV: A Preliminary Case Study from Romania. Medicina, 61.","DOI":"10.3390\/medicina61081468"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"ofae485","DOI":"10.1093\/ofid\/ofae485","article-title":"Antiretroviral Therapy and Cardiovascular Risk in People with HIV in the United States\u2014An Updated Analysis","volume":"11","author":"Sahrmann","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1161\/ATVBAHA.113.302478","article-title":"HIV-1 Matrix Protein P17 Promotes Lymphangiogenesis and Activates the Endothelin-1\/Endothelin B Receptor Axis","volume":"34","author":"Caccuri","year":"2014","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2122050119","DOI":"10.1073\/pnas.2122050119","article-title":"HIV-1 Mutants Expressing B Cell Clonogenic Matrix Protein P17 Variants Are Increasing Their Prevalence Worldwide","volume":"119","author":"Caccuri","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, M., Lin, F., Guo, R., Wu, D., Shen, R., Harypursat, V., Chen, Y., and Chen, Y. (2025). HIV-1 Matrix Protein P17: A Key Factor in HIV-Associated Cancers. Front. Virol., 5.","DOI":"10.3389\/fviro.2025.1584507"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38027","DOI":"10.1038\/srep38027","article-title":"Cellular Aspartyl Proteases Promote the Unconventional Secretion of Biologically Active HIV-1 Matrix Protein P17","volume":"6","author":"Caccuri","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrmicro3490","article-title":"HIV-1 Assembly, Release and Maturation","volume":"13","author":"Freed","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10-1128","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":"ref_17","doi-asserted-by":"crossref","first-page":"100934","DOI":"10.1016\/j.jbc.2021.100934","article-title":"Binding to PI(4,5)P2 Is Indispensable for Secretion of B-Cell Clonogenic HIV-1 Matrix Protein P17 Variants","volume":"297","author":"Bugatti","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1089\/vim.2023.0123","article-title":"Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy","volume":"37","author":"Love","year":"2024","journal-title":"Viral Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41417-020-00246-9","article-title":"B-Cell Clonogenic Activity of HIV-1 P17 Variants Is Driven by PAR1-Mediated EGF Transactivation","volume":"28","author":"Giagulli","year":"2021","journal-title":"Cancer Gene Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s13238-010-0068-0","article-title":"Dynamic Interplay between Viral Adaptation and Immune Recognition during HIV-1 Infection","volume":"1","author":"Motozono","year":"2010","journal-title":"Protein Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sun, N., and Yau, S.S.-T. (2022). In-Depth Investigation of the Point Mutation Pattern of HIV-1. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1033481"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"154061","DOI":"10.1016\/j.prp.2022.154061","article-title":"High Expression of HIV-1 Matrix Protein P17 in Both Lymphoma and Lymph Node Tissues of AIDS Patients","volume":"237","author":"Feng","year":"2022","journal-title":"Pathol.-Res. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Giagulli, C., Marsico, S., Magiera, A.K., Bruno, R., Caccuri, F., Barone, I., Fiorentini, S., And\u00f2, S., and Caruso, A. (2011). Opposite Effects of HIV-1 P17 Variants on PTEN Activation and Cell Growth in B Cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017831"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9972","DOI":"10.1073\/pnas.142274699","article-title":"HIV-1 Matrix Protein P17 Increases the Production of Proinflammatory Cytokines and Counteracts IL-4 Activity by Binding to a Cellular Receptor","volume":"99","author":"Baronio","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bbapap.2007.09.008","article-title":"PI3K\/PTEN Signaling in Tumorigenesis and Angiogenesis","volume":"1784","author":"Jiang","year":"2008","journal-title":"Biochim. Et Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1462-5822.2007.01073.x","article-title":"HIV-1 Matrix Protein P17 Binds to Monocytes and Selectively Stimulates MCP-1 Secretion: Role of Transcriptional Factor AP-1","volume":"10","author":"Marini","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1182\/blood-2011-06-364083","article-title":"HIV-1 Matrix Protein P17 Binds to the IL-8 Receptor CXCR1 and Shows IL-8\u2013like Chemokine Activity on Monocytes through Rho\/ROCK Activation","volume":"119","author":"Giagulli","year":"2012","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.4049\/jimmunol.165.9.5269","article-title":"The CXC Chemokine Receptor 2, CXCR2, Is the Putative Receptor for ELR+ CXC Chemokine-Induced Angiogenic Activity","volume":"165","author":"Addison","year":"2000","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14580","DOI":"10.1073\/pnas.1206605109","article-title":"HIV-1 Matrix Protein P17 Promotes Angiogenesis via Chemokine Receptors CXCR1 and CXCR2","volume":"109","author":"Caccuri","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"ftv062","DOI":"10.1093\/femspd\/ftv062","article-title":"Angiogenic, Lymphangiogenic and Adipogenic Effects of HIV-1 Matrix Protein P17","volume":"73","author":"Basta","year":"2015","journal-title":"Pathog. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e88","DOI":"10.1161\/01.RES.0000099243.20096.FA","article-title":"Paracrine Regulation of Angiogenesis and Adipocyte Differentiation During In Vivo Adipogenesis","volume":"93","author":"Fukumura","year":"2003","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1089\/ten.tea.2009.0635","article-title":"Adipose Tissue Progenitor Cells Directly Interact with Endothelial Cells to Induce Vascular Network Formation","volume":"16","author":"Gollahalli","year":"2010","journal-title":"Tissue Eng. Part A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/s41374-018-0147-z","article-title":"P17 from HIV Induces Brain Endothelial Cell Angiogenesis through EGFR-1-Mediated Cell Signalling Activation","volume":"99","author":"Liu","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bugatti, A., Marsico, S., Mazzuca, P., Schulze, K., Ebensen, T., Giagulli, C., Pe\u00f1a, E., Badim\u00f3n, L., Slevin, M., and Caruso, A. (2020). Role of Autophagy in Von Willebrand Factor Secretion by Endothelial Cells and in the In Vivo Thrombin-Antithrombin Complex Formation Promoted by the HIV-1 Matrix Protein P17. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062022"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/nm.3288","article-title":"Autophagy Regulates Endothelial Cell Processing, Maturation and Secretion of von Willebrand Factor","volume":"19","author":"Torisu","year":"2013","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10850","DOI":"10.1074\/jbc.M109.080796","article-title":"Dual Role of 3-Methyladenine in Modulation of Autophagy via Different Temporal Patterns of Inhibition on Class I and III Phosphoinositide 3-Kinase","volume":"285","author":"Wu","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14807","DOI":"10.1073\/pnas.0506857102","article-title":"Persistence of HIV-1 Structural Proteins and Glycoproteins in Lymph Nodes of Patients under Highly Active Antiretroviral Therapy","volume":"102","author":"Popovic","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14331","DOI":"10.1073\/pnas.1514748112","article-title":"Role of HIV-1 Matrix Protein P17 Variants in Lymphoma Pathogenesis","volume":"112","author":"Dolcetti","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/hon.2562","article-title":"Lymphomagenic Properties of a HIV P17 Variant Derived from a Splenic Marginal Zone Lymphoma Occurred in a HIV-infected Patient","volume":"37","author":"Caccuri","year":"2019","journal-title":"Hematol. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1002\/ijc.29494","article-title":"A Natural HIV P17 Protein Variant Up-Regulates the LMP-1 EBV Oncoprotein and Promotes the Growth of EBV-Infected B-Lymphocytes: Implications for EBV-Driven Lymphomagenesis in the HIV Setting: HIV P17 and EBV-Driven Lymphomagenesis","volume":"137","author":"Martorelli","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1093\/infdis\/jir134","article-title":"Higher Levels of CRP, D-Dimer, IL-6, and Hyaluronic Acid Before Initiation of Antiretroviral Therapy (ART) Are Associated with Increased Risk of AIDS or Death","volume":"203","author":"Boulware","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.clim.2010.02.010","article-title":"D-Dimer and CRP Levels Are Elevated Prior to Antiretroviral Treatment in Patients Who Develop IRIS","volume":"136","author":"Porter","year":"2010","journal-title":"Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1086\/605447","article-title":"The INSIGHT Strategies for Management of Antiretroviral Therapy (SMART) Study Group. Activation and Coagulation Biomarkers Are Independent Predictors of the Development of Opportunistic Disease in Patients with HIV Infection","volume":"200","author":"Rodger","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1001\/archinte.166.1.64","article-title":"C-Reactive Protein Is a Marker for Human Immunodeficiency Virus Disease Progression","volume":"166","author":"Lau","year":"2006","journal-title":"Arch. Intern. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e01200-21","DOI":"10.1128\/JVI.01200-21","article-title":"The HIV-1 Matrix Protein P17 Does Cross the Blood-Brain Barrier","volume":"96","author":"Caccuri","year":"2022","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10313","DOI":"10.1038\/s41598-017-10875-0","article-title":"HIV-1 Matrix Protein P17 Misfolding Forms Toxic Amyloidogenic Assemblies That Induce Neurocognitive Disorders","volume":"7","author":"Zeinolabediny","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/BF00294238","article-title":"Human Immunodeficiency Virus (HIV) Envelope and Core Proteins in CNS Tissues of Patients with the Acquired Immune Deficiency Syndrome (AIDS)","volume":"79","author":"Budka","year":"1990","journal-title":"Acta Neuropathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1365-2990.1991.tb00707.x","article-title":"Multifocal Multinucleated Giant Cell Myelitis in an AIDS Patient","volume":"17","author":"Geny","year":"1991","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1097\/00002030-199811000-00014","article-title":"Elevated Cerebrospinal Fluid Levels of Monocyte Chemotactic Protein-1 Correlate with HIV-1 Encephalitis and Local Viral Replication","volume":"12","author":"Cinque","year":"1998","journal-title":"AIDS"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1073\/pnas.95.6.3117","article-title":"Induction of Monocyte Chemoattractant Protein-1 in HIV-1 Tat-Stimulated Astrocytes and Elevation in AIDS Dementia","volume":"95","author":"Conant","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9214","DOI":"10.1128\/JVI.74.19.9214-9221.2000","article-title":"Induction of the Chemokines Interleukin-8 and IP-10 by Human Immunodeficiency Virus Type 1 Tat in Astrocytes","volume":"74","author":"Kutsch","year":"2000","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8195","DOI":"10.1128\/JVI.75.17.8195-8202.2001","article-title":"Interleukin-8 Stimulates Human Immunodeficiency Virus Type 1 Replication and Is a Potential New Target for Antiretroviral Therapy","volume":"75","author":"Lane","year":"2001","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1073\/pnas.93.7.3099","article-title":"Crystal Structures of the Trimeric Human Immunodeficiency Virus Type 1 Matrix Protein: Implications for Membrane Association and Assembly","volume":"93","author":"Hill","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1006\/jmbi.1994.1719","article-title":"Three-Dimensional Structure of the Human Immunodeficiency Virus Type 1 Matrix Protein","volume":"244","author":"Massiah","year":"1994","journal-title":"J. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1742-4690-2-18","article-title":"BioAfrica\u2019s HIV-1 Proteomics Resource: Combining Protein Data with Bioinformatics Tools","volume":"2","author":"Doherty","year":"2005","journal-title":"Retrovirology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Choi, H.-J., Jeong, Y.J., Kim, J., and Hoe, H.-S. (2023). EGFR Is a Potential Dual Molecular Target for Cancer and Alzheimer\u2019s Disease. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1238639"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.4103\/1673-5374.332132","article-title":"Repurposed Anti-Cancer Epidermal Growth Factor Receptor Inhibitors: Mechanisms of Neuroprotective Effects in Alzheimer\u2019s Disease","volume":"17","author":"Mansour","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_58","unstructured":"Kemnic, T., and Gulick, P. (2025). HIV Antiretroviral Therapy. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Weichseldorfer, M., Reitz, M., and Latinovic, O.S. (2021). Past HIV-1 Medications and the Current Status of Combined Antiretroviral Therapy Options for HIV-1 Patients. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111798"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1001\/jama.2024.24543","article-title":"Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society\u2013USA Panel","volume":"333","author":"Gandhi","year":"2025","journal-title":"JAMA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"ofaf446","DOI":"10.1093\/ofid\/ofaf446","article-title":"HIV-1 Drug Resistance Trends in the Era of Modern Antiretrovirals: 2018\u20132024","volume":"12","author":"Kagan","year":"2025","journal-title":"Open Forum Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1007\/s40121-025-01229-9","article-title":"The Role of Protease Inhibitors in HIV Treatment: Who Still Needs Them in 2025?","volume":"14","author":"Sempere","year":"2025","journal-title":"Infect. Dis. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"106898","DOI":"10.1016\/j.phrs.2023.106898","article-title":"Pillars of Long-Term Antiretroviral Therapy Success","volume":"196","author":"Taramasso","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Kanmogne, G.D. (2024). HIV Infection, Antiretroviral Drugs, and the Vascular Endothelium. Cells, 13.","DOI":"10.3390\/cells13080672"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e2010034","DOI":"10.4084\/mjhid.2010.034","article-title":"HIV Infection, Antiretroviral Therapy and Cardiovascular Risk","volume":"2","author":"Cauda","year":"2010","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/QAI.0b013e31818ceaa4","article-title":"Cardiovascular Complications in HIV Management: Past, Present, and Future","volume":"50","author":"Aberg","year":"2009","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"107812","DOI":"10.1016\/j.phrs.2025.107812","article-title":"HIV Infection, Antiretroviral Therapy and Vascular Dysfunction: Effects, Mechanisms and Treatments","volume":"217","author":"Wei","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.atherosclerosis.2008.02.003","article-title":"High-Sensitivity C-Reactive Protein Levels in HIV-Infected Patients Treated or Not with Antiretroviral Drugs and Their Correlation with Factors Related to Cardiovascular Risk and HIV Infection","volume":"201","author":"Greco","year":"2008","journal-title":"Atherosclerosis"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mabhida, S.E., Mchiza, Z.J., Mokgalaboni, K., Hanser, S., Choshi, J., Mokoena, H., Ziqubu, K., Masilela, C., Nkambule, B.B., and Ndwandwe, D.E. (2024). High-Sensitivity C-Reactive Protein among People Living with HIV on Highly Active Antiretroviral Therapy: A Systemic Review and Meta-Analysis. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09050-4"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Di Yacovo, S., Saumoy, M., S\u00e1nchez-Quesada, J.L., Navarro, A., Sviridov, D., Javaloyas, M., Vila, R., Vernet, A., Low, H., and Pe\u00f1afiel, J. (2020). Lipids, Biomarkers, and Subclinical Atherosclerosis in Treatment-Naive HIV Patients Starting or Not Starting Antiretroviral Therapy: Comparison with a Healthy Control Group in a 2-Year Prospective Study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0237739"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1310\/hct1204-215","article-title":"Assessment of Vascular Function in HIV-Infected Patients","volume":"12","author":"Borges","year":"2011","journal-title":"HIV Clin. Trials"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.atherosclerosis.2006.12.022","article-title":"Both Long-Term HIV Infection and Highly Active Antiretroviral Therapy Are Independent Risk Factors for Early Carotid Atherosclerosis","volume":"196","author":"Lorenz","year":"2008","journal-title":"Atherosclerosis"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1161\/STROKEAHA.110.583856","article-title":"Association between Human Immunodeficiency Virus Infection and Stiffness of the Common Carotid Artery","volume":"41","author":"Seaberg","year":"2010","journal-title":"Stroke"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1007\/s11684-017-0592-x","article-title":"Irreversible Phenotypic Perturbation and Functional Impairment of B Cells during HIV-1 Infection","volume":"11","author":"Yan","year":"2017","journal-title":"Front. Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Anand, A.R., Rachel, G., and Parthasarathy, D. (2018). HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00185"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chandran, S., Adler, M., Chen, L., Kaur, S., and Dhillon, N.K. (2025). HIV-Tat and Vascular Endothelium: Implications in the HIV Associated Brain, Heart, and Lung Complications. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1621338"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Garcia, A.K., Lujea, N.C., Baig, J., Heath, E., Nguyen, M.T., Rodriguez, M., Campbell, P., Castro Piedras, I., Suarez Martinez, E., and Almodovar, S. (2025). Differential Effects of Human Immunodeficiency Virus Nef Variants on Pulmonary Vascular Endothelial Cell Dysfunction. Infect. Dis. Rep., 17.","DOI":"10.3390\/idr17030065"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12967-018-1500-0","article-title":"The Role of HIV Tat Protein in HIV-Related Cardiovascular Diseases","volume":"16","author":"Jiang","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Cafaro, A., Schietroma, I., Sernicola, L., Belli, R., Campagna, M., Mancini, F., Farcomeni, S., Pavone-Cossut, M.R., Borsetti, A., and Monini, P. (2024). Role of HIV-1 Tat Protein Interactions with Host Receptors in HIV Infection and Pathogenesis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031704"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"27569","DOI":"10.18632\/oncotarget.15174","article-title":"Tat Is a Multifunctional Viral Protein That Modulates Cellular Gene Expression and Functions","volume":"8","author":"Clark","year":"2017","journal-title":"Oncotarget"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1038\/s41598-019-39531-5","article-title":"A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation","volume":"9","author":"Ruiz","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Mele, A.R., Marino, J., Dampier, W., Wigdahl, B., and Nonnemacher, M.R. (2020). HIV-1 Tat Length: Comparative and Functional Considerations. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00444"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/febs.13168","article-title":"Tat Predominantly Associates with Host Promoter Elements in HIV -1-infected T-cells\u2013Regulatory Basis of Transcriptional Repression of c-Rel","volume":"282","author":"Dhamija","year":"2015","journal-title":"FEBS J."},{"key":"ref_84","first-page":"217","article-title":"Sequential Steps in Tat Trans-Activation of HIV-1 Mediated through Cellular DNA, RNA, and Protein Binding Factors","volume":"5","author":"Gatignol","year":"1996","journal-title":"Gene Expr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1600-0854.2011.01286.x","article-title":"The Ins and Outs of HIV-1 Tat","volume":"13","author":"Debaisieux","year":"2012","journal-title":"Traffic"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7","DOI":"10.21037\/arh.2019.02.01","article-title":"Endothelial Dysfunction in HIV Infection: Experimental and Clinical Evidence on the Role of Oxidative Stress","volume":"3","author":"Margaritis","year":"2019","journal-title":"Ann. Res. Hosp."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"14390","DOI":"10.1074\/jbc.M108591200","article-title":"The Human Immunodeficiency Virus-1 Tat Protein Activates Human Umbilical Vein Endothelial Cell E-Selectin Expression via an NF-\u03baB-Dependent Mechanism","volume":"277","author":"Flores","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_88","first-page":"1535","article-title":"Human Immunodeficiency Virus-1-Tat Protein Induces the Cell Surface Expression of Endothelial Leukocyte Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Intercellular Adhesion Molecule-1 in Human Endothelial Cells","volume":"90","author":"Dhawan","year":"1997","journal-title":"Blood"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.4049\/jimmunol.166.2.1380","article-title":"HIV-1 Tat Protein Stimulates In Vivo Vascular Permeability and Lymphomononuclear Cell Recruitment","volume":"166","author":"Arese","year":"2001","journal-title":"J. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Kovacs, L., Bruder-Nascimento, T., Greene, L., Kennard, S., and Belin de Chantem\u00e8le, E.J. (2021). Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010977"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.freeradbiomed.2010.12.019","article-title":"Nox2-Based NADPH Oxidase Mediates HIV-1 Tat-Induced up-Regulation of VCAM-1\/ICAM-1 and Subsequent Monocyte Adhesion in Human Astrocytes","volume":"50","author":"Song","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.neulet.2016.12.073","article-title":"HIV-1 Tat Disrupts Blood-Brain Barrier Integrity and Increases Phagocytic Perivascular Macrophages and Microglia in the Dorsal Striatum of Transgenic Mice","volume":"640","author":"Leibrand","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Basmaciogullari, S., and Pizzato, M. (2014). The Activity of Nef on HIV-1 Infectivity. Front. Microbiol., 5.","DOI":"10.3389\/fmicb.2014.00232"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"15158","DOI":"10.1074\/jbc.REV120.012317","article-title":"Structure, Function, and Inhibitor Targeting of HIV-1 Nef-Effector Kinase Complexes","volume":"295","author":"Staudt","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e0028025","DOI":"10.1128\/jvi.00280-25","article-title":"HIV-1 Nef Activates Proviral DNA Transcription by Recruiting Src Kinase to Phosphorylate Host Protein Nef-Associated Factor 1 to Compromise Its Viral Restrictive Function","volume":"99","author":"Fan","year":"2025","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/boc.202100027","article-title":"HIV-1 Nef Hijacks Both Exocytic and Endocytic Pathways of Host Intracellular Trafficking through Differential Regulation of Rab GTPases","volume":"114","author":"Kumari","year":"2022","journal-title":"Biol. Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"37021","DOI":"10.1038\/srep37021","article-title":"HIV-1 Nef Sequesters MHC-I Intracellularly by Targeting Early Stages of Endocytosis and Recycling","volume":"6","author":"Dirk","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Scuderi, G., Fagone, P., Petralia, M.C., Nicoletti, F., and Basile, M.S. (2025). Multifaceted Role of Nef in HIV-Associated Neurocognitive Disorder: Histopathological Alterations and Underlying Mechanisms. Brain Sci., 15.","DOI":"10.3390\/brainsci15090987"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Wang, T., Green, L.A., Gupta, S.K., Kim, C., Wang, L., Almodovar, S., Flores, S.C., Prudovsky, I.A., Jolicoeur, P., and Liu, Z. (2014). Transfer of Intracellular HIV Nef to Endothelium Causes Endothelial Dysfunction. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091063"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1161\/CIRCRESAHA.119.315082","article-title":"HIV-Nef Protein Transfer to Endothelial Cells Requires Rac1 Activation and Leads to Endothelial Dysfunction Implications for Statin Treatment in HIV Patients","volume":"125","author":"Chelvanambi","year":"2019","journal-title":"Circ. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jss.2009.02.005","article-title":"HIV Nef Protein Causes Endothelial Dysfunction in Porcine Pulmonary Arteries and Human Pulmonary Artery Endothelial Cells","volume":"156","author":"Duffy","year":"2009","journal-title":"J. Surg. Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Rivera, J., Isidro, R.A., Loucil-Alicea, R.Y., Cruz, M.L., Appleyard, C.B., Isidro, A.A., Chompre, G., Colon-Rivera, K., and Noel, R.J. (2019). Infusion of HIV-1 Nef-Expressing Astrocytes into the Rat Hippocampus Induces Enteropathy and Interstitial Pneumonitis and Increases Blood\u2013Brain-Barrier Permeability. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225760"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.nbd.2012.08.007","article-title":"Astrocytic Expression of HIV-1 Nef Impairs Spatial and Recognition Memory","volume":"49","author":"Chompre","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s12974-024-03124-5","article-title":"Extracellular Vesicles Produced by HIV-1 Nef-Expressing Cells Induce Myelin Impairment and Oligodendrocyte Damage in the Mouse Central Nervous System","volume":"21","author":"Schenck","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/bip.20130","article-title":"Preclinical Studies on Immunogenicity of the HIV-1 P17-based Synthetic Peptide AT20-KLH","volume":"76","author":"Fiorentini","year":"2004","journal-title":"Biopolymers"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4758","DOI":"10.1016\/j.vaccine.2008.06.082","article-title":"Synthetic Peptide AT20 Coupled to KLH Elicits Antibodies against a Conserved Conformational Epitope from a Major Functional Area of the HIV-1 Matrix Protein P17","volume":"26","author":"Fiorentini","year":"2008","journal-title":"Vaccine"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.pharmthera.2010.08.005","article-title":"HIV-1 Matrix Protein P17: A Candidate Antigen for Therapeutic Vaccines against AIDS","volume":"128","author":"Fiorentini","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.vaccine.2013.12.051","article-title":"Synthetic HIV-1 Matrix Protein P17-Based AT20-KLH Therapeutic Immunization in HIV-1-Infected Patients Receiving Antiretroviral Treatment: A Phase I Safety and Immunogenicity Study","volume":"32","author":"Iaria","year":"2014","journal-title":"Vaccine"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1179\/1528433614Z.0000000018","article-title":"Long-Lasting Humoral Immune Response Induced in HIV-1-Infected Patients by a Synthetic Peptide (AT20) Derived from the HIV-1 Matrix Protein P17 Functional Epitope","volume":"16","author":"Iaria","year":"2015","journal-title":"HIV Clin. Trials"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Verrier, B., Paul, S., Terrat, C., Bastide, L., Ensinas, A., Phelip, C., Chanut, B., Bulens-Grassigny, L., Jospin, F., and Guillon, C. (2017). Exploiting Natural Cross-Reactivity between Human Immunodeficiency Virus (HIV)-1 P17 Protein and Anti-Gp41 2F5 Antibody to Induce HIV-1 Neutralizing Responses In Vivo. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00770"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11949\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:32:58Z","timestamp":1765805578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":110,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411949"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411949","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]}}}