{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:52:14Z","timestamp":1790711534091,"version":"4.1.0"},"reference-count":128,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA048439"],"award-info":[{"award-number":["DA048439"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: In the United States, the illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis. Synthetic opioids are known to enhance viral replication and to suppress immunologic responses, but their effects on HIV pathogenesis remain unclear. Thus, we examined the impact of fentanyl on HIV-susceptible and HIV-infected cell types. Methods: TZM-bl and HIV-infected lymphocyte cells were incubated with fentanyl at varying concentrations. Expression levels of the CXCR4 and CCR5 chemokine receptors and HIV p24 antigen were quantified with ELISA. HIV proviral DNA was quantified using SYBR RT-PCR. Cell viability was detected with the MTT assay. RNAseq was performed to characterize cellular gene regulation in the presence of fentanyl. Results: Fentanyl enhanced expression of both chemokine receptor levels in a dose-dependent manner in HIV-susceptible and infected cell lines. Similarly, fentanyl induced viral expression in HIV-exposed TZM-bl cells and in HIV-infected lymphocyte cell lines. Multiple genes associated with apoptosis, antiviral\/interferon response, chemokine signaling, and NF\u03baB signaling were differentially regulated. Conclusions: Synthetic opioid fentanyl impacts HIV replication and chemokine co-receptor expression. Increased virus levels suggest that opioid use may increase the likelihood of transmission and accelerate disease progression.<\/jats:p>","DOI":"10.3390\/v15041027","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T10:11:25Z","timestamp":1682071885000},"page":"1027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Synthetic Opioid Fentanyl Increases HIV Replication and Chemokine Co-Receptor Expression in Lymphocyte Cell Lines"],"prefix":"10.3390","volume":"15","author":[{"given":"Janani","family":"Madhuravasal Krishnan","sequence":"first","affiliation":[{"name":"Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Kong","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Karns","sequence":"additional","affiliation":[{"name":"Digestive Health Center, Cincinnati Children\u2019s Hospital, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Medvedovic","sequence":"additional","affiliation":[{"name":"Department of Environmental & Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Center for Addiction Research, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2876-3811","authenticated-orcid":false,"given":"Jason T.","family":"Blackard","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Center for Addiction Research, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.15585\/mmwr.mm6634a2","article-title":"Trends in deaths involving heroin and synthetic opioids excluding methadone, and law enforcement drug product reports, by census region\u2014United States, 2006\u20132015","volume":"66","author":"Gladden","year":"2017","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.15585\/mmwr.mm7006a4","article-title":"Trends and geographic patterns in drug and synthetic opioid overdose deaths\u2014United States, 2013\u20132019","volume":"70","author":"Mattson","year":"2021","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"904","DOI":"10.15585\/mmwr.mm6634a3","article-title":"Overdose deaths related to fentanyl and its analogs\u2014Ohio, January\u2013February 2017","volume":"66","author":"Daniulaityte","year":"2017","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"844","DOI":"10.15585\/mmwr.mm6533a3","article-title":"Increases in fentanyl-related overdose deaths\u2014Florida and Ohio, 2013\u20132015","volume":"65","author":"Peterson","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1021\/acsomega.7b01536","article-title":"LC-MS\/MS-based method for the multiplex detection of 24 fentanyl analogues and metabolites in whole blood at sub ng mL-1 concentrations","volume":"3","author":"Strayer","year":"2018","journal-title":"ACS Omega"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102989","DOI":"10.1016\/j.drugpo.2020.102989","article-title":"Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada","volume":"86","author":"Samji","year":"2020","journal-title":"Int. J. Drug Policy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s13365-011-0037-2","article-title":"Role of mu-opioid receptors as cofactors in human immunodeificiency virus type 1 disease progression and neuorpathogenesis","volume":"17","author":"Banerjee","year":"2011","journal-title":"J. Neuroviral."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.3389\/fimmu.2019.02904","article-title":"The role of opioid receptors in immune system function","volume":"10","author":"Eisenstein","year":"2019","journal-title":"Front Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1124\/mol.64.4.876","article-title":"The role of nuclear factor kappaB in tumor necrosis factor-regulated transcription of the human mu-opioid receptor gene","volume":"64","author":"Kraus","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1111\/bph.13750","article-title":"Opioids and the immune system\u2014Friend or foe","volume":"175","author":"Plein","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","first-page":"5","article-title":"Opioid system modulates the immune function: A review","volume":"1","author":"Liang","year":"2016","journal-title":"Transl. Perioper. Pain Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Brejchova, J., Holan, V., and Svoboda, P. (2021). Expression of opioid receptors in cells of the immune system. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010315"},{"key":"ref_13","unstructured":"Fentanyl Drug Facts (2022, January 10). National Institute on Drug Abuse: 2021, Available online: https:\/\/www.drugabuse.gov\/publications\/drugfacts\/fentanyl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.drugpo.2019.10.004","article-title":"Associations between perceived illicit fentanyl use and infectious disease risks among people who inject drugs","volume":"74","author":"Lambdin","year":"2019","journal-title":"Int. J. Drug Policy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"94","DOI":"10.2174\/1570162X17666190618154534","article-title":"Synthetic opioid use and common injection-associated viruses: Expanding the translational research agenda","volume":"17","author":"Blackard","year":"2019","journal-title":"Curr. HIV Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"970","DOI":"10.3389\/fmicb.2016.00970","article-title":"Opioids and viral infections: A double-edged sword","volume":"7","author":"Tahamtan","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/iji.12485","article-title":"CCR5 and CCR5\u039432 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box","volume":"47","author":"Ellwanger","year":"2020","journal-title":"Int. J. Immunogenet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.imlet.2016.06.006","article-title":"CXCR4 signaling in health and disease","volume":"177","author":"Pozzobon","year":"2016","journal-title":"Immunol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, X., Ye, L., Li, J., Song, L., Fulambarkar, N., and Ho, W. (2012). Morphine Suppresses IFN Signaling Pathway and Enhances AIDS Virus Infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031167"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.bbi.2007.01.011","article-title":"Neurobiology of HIV, psychiatric and substance abuse comorbidity research: Workshop report","volume":"21","author":"Kopnisky","year":"2007","journal-title":"Brain Behav. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1136\/jim-50-06-03","article-title":"Morphine enhances HIV infection of human blood mononuclear phagocytes through modulation of beta-chemokines and CCR5 receptor","volume":"50","author":"Guo","year":"2002","journal-title":"J. Investig. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1203\/01.PDR.0000074973.83826.4C","article-title":"Morphine Enhances HIV Infection of Neonatal Macrophages","volume":"54","author":"Li","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1097\/00002030-199009000-00006","article-title":"Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures","volume":"4","author":"Peterson","year":"1990","journal-title":"AIDS"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0923-2516(91)90056-9","article-title":"Morphine stimulates HIV replication in primary cultures of human Kupffer cells","volume":"142","author":"Schweitzer","year":"1991","journal-title":"Res. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1086\/340816","article-title":"Morphine promotes simian acquired immunodeficiency syndrome virus replication in monkey peripheral mononuclear cells: Induction of CC chemokine receptor 5 expression for virus entry","volume":"185","author":"Suzuki","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0165-5728(94)90043-4","article-title":"Morphine amplifies HIV-1 expression in chronically infected promonocytes cocultured with human brain cells","volume":"50","author":"Peterson","year":"1994","journal-title":"J. Neuroimmunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1128\/cdli.4.2.127-132.1997","article-title":"Immunoregulatory effects of morphine on human lymphocytes","volume":"4","author":"Nair","year":"1997","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/glia.20262","article-title":"HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokines","volume":"53","author":"Wu","year":"2006","journal-title":"Glia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1189\/jlb.0305167","article-title":"Morphine inhibits CD8+ T cell-mediated, noncytolytic, anti-HIV activity in latently infected immune cells","volume":"78","author":"Wang","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1089\/aid.1990.6.1163","article-title":"Morphine-Induced Transactivation of HIV-1 LTR in Human Neuroblastoma Cells. AIDS Res","volume":"6","author":"Squinto","year":"1990","journal-title":"Hum. Retrovir."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/0-306-47611-8_28","article-title":"Effect of cocaine on chemokine and CCR-5 gene expression by mononuclear cells from normal donors and HIV-1 infected patients","volume":"493","author":"Nair","year":"2001","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.drugalcdep.2015.12.027","article-title":"In vivo effects of methamphetamine on HIV-1 replication: A population-based study","volume":"159","author":"Jiang","year":"2016","journal-title":"Drug Alcohol Depend."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8358","DOI":"10.1128\/JVI.74.18.8358-8367.2000","article-title":"Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120","volume":"74","author":"Derdeyn","year":"2000","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12585","DOI":"10.1128\/JVI.01726-08","article-title":"Identification of gamma retroviruses constitutively released from cell lines used for human immunodeficiency virus research","volume":"82","author":"Takeuchi","year":"2008","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1093\/emboj\/cdg188","article-title":"HIV reproducibly establishes a latent infection after acute infection of T cells in vitro","volume":"22","author":"Jordan","year":"2003","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1093\/emboj\/20.7.1726","article-title":"The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation","volume":"20","author":"Jordan","year":"2001","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1089\/aid.1989.5.253","article-title":"Origin of the HIV-susceptible human CD4+ cell line H9","volume":"5","author":"Mann","year":"1989","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"431","DOI":"10.4049\/jimmunol.142.2.431","article-title":"Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone","volume":"142","author":"Clouse","year":"1989","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropharm.2017.10.016","article-title":"Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review","volume":"134","author":"Armenian","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S1386-6532(03)00169-0","article-title":"Quantitative detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA in peripheral blood mononuclear cells by SYBR green real-time PCR technique","volume":"29","author":"Gibellini","year":"2004","journal-title":"J. Clin. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/15476286.2018.1564465","article-title":"Balancing yield, purity and practicality: A modified differential ultracentrifugation protocol for efficient isolation of small extracellular vesicles from human serum","volume":"16","author":"Langevin","year":"2019","journal-title":"RNA Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/bioinformatics\/bty633","article-title":"ape 5.0: An environment for modern phylogenetics and evolutionary analyses in R","volume":"35","author":"Paradis","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nmeth.3252","article-title":"Orchestrating high-throughput genomic analysis with Bioconductor","volume":"12","author":"Huber","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/nar\/gkt1181","article-title":"miRBase: Annotating high confidence microRNAs using deep sequencing data","volume":"42","author":"Kozomara","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: Differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1089\/dna.2018.4550","article-title":"Intracerebral hemorrhage induces inflammatory gene expression in peripheral blood: Global transcriptional profiling in intracerebral hemorrhage patients","volume":"38","author":"Walsh","year":"2019","journal-title":"DNA Cell Biol."},{"key":"ref_48","first-page":"104","article-title":"Varying negative pressure wound therapy acute effects on human split-thickness autografts","volume":"41","author":"Rapp","year":"2020","journal-title":"J. Burn. Care Res."},{"key":"ref_49","unstructured":"(2022, May 11). U.S. Overdose Deaths In 2021 Increased Half as Much as in 2020\u2014But Are Still Up 15% 2022.2022), Available online: https:\/\/www.cdc.gov\/nchs\/pressroom\/nchs_press_releases\/2022\/202205.htm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1053\/j.semperi.2019.01.001","article-title":"The United States opioid epidemic","volume":"43","author":"Lyden","year":"2019","journal-title":"Semin. Perinatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.ccc.2020.07.006","article-title":"Impact of the Opioid Epidemic","volume":"36","author":"Lavonas","year":"2020","journal-title":"Crit. Care Clin."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1177\/0363546519836727","article-title":"Opioid epidemic","volume":"47","author":"Reider","year":"2019","journal-title":"Am. J. Sports Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41380-020-0661-4","article-title":"The changing opioid crisis: Development, challenges and opportunities","volume":"26","author":"Volkow","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0140-6736(16)00619-X","article-title":"Public health and international drug policy","volume":"387","author":"Csete","year":"2016","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1097\/QAI.0000000000002062","article-title":"Sharing of injection drug preparation equipment is associated with HIV infection: A cross-sectional study","volume":"81","author":"Ball","year":"2019","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s10461-009-9631-1","article-title":"Syringe-mediated syndemics","volume":"15","author":"Bulled","year":"2011","journal-title":"AIDS Behav."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s13365-015-0398-z","article-title":"The effects of cocaine on HIV transcription","volume":"22","author":"Tyagi","year":"2016","journal-title":"J. Neurovirol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.drugpo.2019.09.018","article-title":"Drug use and risk behaviour profile, and the prevalence of HIV, hepatitis C and hepatitis B among people with methamphetamine use in Iran","volume":"73","author":"Moradi","year":"2019","journal-title":"Int. J. Drug Policy"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e1192","DOI":"10.1016\/S2214-109X(17)30375-3","article-title":"Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: A multistage systematic review","volume":"5","author":"Degenhardt","year":"2017","journal-title":"Lancet Glob. Health"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s11481-020-09928-5","article-title":"HIV Infection and Neurocognitive Disorders in the Context of Chronic Drug Abuse: Evidence for Divergent Findings Dependent upon Prior Drug History","volume":"15","author":"Illenberger","year":"2020","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cernasev, A., Veve, M.P., Cory, T.J., Summers, N.A., Miller, M., Kodidela, S., and Kumar, S. (2020). Opioid Use Disorders in People Living with HIV\/AIDS: A Review of Implications for Patient Outcomes, Drug Interactions, and Neurocognitive Disorders. Pharmacy, 8.","DOI":"10.3390\/pharmacy8030168"},{"key":"ref_62","unstructured":"Saxon, A., and Hermann, R. (2018). Opioid Use Disorder: Epidemiology, Pharmacology, Clinical Manifestations, Course, Screening, Assessment, and Diagnosis, Wolters Kluwer, UpToDate."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/QAI.0000000000000591","article-title":"Long-term Prescription of Opioids and\/or Benzodiazepines and Mortality among HIV-Infected and Uninfected Patients","volume":"69","author":"Weisberg","year":"2015","journal-title":"J Acquir. Immune Defic. Syndr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0165-5728(95)00089-K","article-title":"beta-Endorphin enhances the replication of neurotropic human immunodeficiency virus in fetal perivascular microglia","volume":"61","author":"Sundar","year":"1995","journal-title":"J. Neuroimmunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0028-3908(98)00167-1","article-title":"Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures: Implication of an atypical mu-opioid receptor","volume":"38","author":"Peterson","year":"1999","journal-title":"Neuropharmacology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/0006-2952(95)00176-Z","article-title":"Upregulation of HIV-1 expression in cocultures of chronically infected promonocytes and human brain cells by dynorphin","volume":"50","author":"Chao","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1742-6405-11-17","article-title":"The effects of opioids on HIV reactivation in latently-infected T-lymphoblasts","volume":"11","author":"Prottengeier","year":"2014","journal-title":"AIDS Res. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"739","DOI":"10.4049\/jimmunol.177.1.739","article-title":"Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B","volume":"177","author":"Xu","year":"2006","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.3389\/fimmu.2019.02601","article-title":"MorphineWithdrawal Enhances HIV Infection of Macrophages","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_70","first-page":"1077","article-title":"Activation of the -opioid receptor inhibits serum deprivation induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway","volume":"28","author":"Tang","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.3389\/fmicb.2015.01230","article-title":"Heroin inhibits HIV-restriction miRNAs and enhances HIV infection of macrophages","volume":"6","author":"Wang","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s11481-019-09892-9","article-title":"Heroin Abuse and\/or HIV Infection Dysregulate Plasma Exosomal miRNAs","volume":"15","author":"Wang","year":"2020","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Gornalusse, G.G., Vojtech, L.N., Levy, C.N., Hughes, S.M., Kim, Y., Valdez, R., Pandey, U., Ochsenbauer, C., Astronomo, R., and McElrath, J. (2021). Buprenorphine Increases HIV-1 Infection In Vitro but Does Not Reactivate HIV-1 from Latency. Viruses, 13.","DOI":"10.3390\/v13081472"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1086\/338011","article-title":"Methadone enhances human immunodeficiency virus infection of human immune cells","volume":"185","author":"Wang","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.3389\/fimmu.2020.01253","article-title":"Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_76","unstructured":"Facts about Fentanyl (2023, March 20). DEA, United States Drug Enforcement Administration: 2021, Available online: https:\/\/www.dea.gov\/resources\/facts-about-fentany."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1556-4029.2007.00597.x","article-title":"Oral abuse of fentanyl patches (Duragesic\u00ae): Seven case reports","volume":"53","author":"Woodall","year":"2008","journal-title":"J. Forensic Sci."},{"key":"ref_78","first-page":"289","article-title":"Metabolic patterns of fentanyl, meperidine, methylphenidate, tapentadol and tramadol observed in urine, serum or plasma","volume":"41","author":"Wu","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Kong, L., Karns, R., Shata, M., Brown, J.L., Lyons, M.S., Sherman, K.E., and Blackard, J.T. (2021). The synthetic opioid fentanyl enhances viral replication in vitro. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0249581"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.3892\/ijo.2013.2046","article-title":"Upregulation of the opioid receptor in liver cancer promotes liver cancer progression both in vitro and in vivo","volume":"43","author":"Tang","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.3892\/or.2013.2640","article-title":"In vivo and in vitro inhibition of human liver cancer progress by downregulation of the \u03bc-opioid receptor and relevant mechanisms","volume":"30","author":"Lu","year":"2013","journal-title":"Oncol. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1007\/s10620-011-1659-1","article-title":"Prospective Evaluation of FibroScan for the Diagnosis of Hepatic Fibrosis Compared with Liver Biopsy\/AST Platelet Ratio Index and FIB-4 in Patients with Chronic HBV Infection","volume":"56","author":"Zhu","year":"2011","journal-title":"Dig. Dis. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"839","DOI":"10.3892\/mmr.2014.2301","article-title":"Activated-opioid receptors inhibit hydrogen peroxideinduced apoptosis in liver cancer cells through the PKC\/ERK signaling pathwa","volume":"10","author":"Jia","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1136\/gut.2007.120303","article-title":"Role of endogenous opioids in modulating HSC activity in vitro and liver fibrosis in vivo","volume":"57","author":"Candelaresi","year":"2008","journal-title":"Gut"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1365-2893.2007.00940.x","article-title":"Methamphetamine enhances Hepatitis C virus replication in human hepatocytes","volume":"15","author":"Ye","year":"2008","journal-title":"J. Viral Hepat."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1136\/gut.2003.034223","article-title":"Survey of hepatitis B surface variant infection in children 15 years after a nationwide vaccination programme in Taiwan","volume":"53","author":"Hsu","year":"2004","journal-title":"Gut"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.2353\/ajpath.2008.070971","article-title":"Methamphetamine Enhances HIV Infection of Macrophages","volume":"172","author":"Liang","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0042-6822(02)00031-4","article-title":"HIV-1 infection in peripheral blood lymphocytes (PBLs) exposed to alcohol","volume":"307","author":"Liu","year":"2003","journal-title":"Virology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1128\/CDLI.7.1.96-100.2000","article-title":"Cocaine differentially modulates chemokine production by mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients","volume":"7","author":"Nair","year":"2000","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.lfs.2010.09.019","article-title":"Effect of methamphetamine on expression of HIV coreceptors and CC-chemokines by dendritic cells","volume":"88","author":"Nair","year":"2011","journal-title":"Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s11481-008-9128-0","article-title":"Methamphetamine enhances HIV-1 infectivity in monocyte derived dendritic cells","volume":"4","author":"Nair","year":"2009","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1189\/jlb.0405219","article-title":"Cocaine and -1 receptors modulate HIV infection, chemokine receptors, and the HPA axis in the huPBL-SCID model","volume":"78","author":"Roth","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1111\/j.1530-0277.2002.tb02496.x","article-title":"Alcohol potentiates HIV-1 infection of human blood mononuclear phagocytes","volume":"26","author":"Wang","year":"2002","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"31305","DOI":"10.1074\/jbc.M001269200","article-title":"Morphine induces gene expression of CCR5 in human CEM x174 lymphocytes","volume":"275","author":"Miyagi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S1359-6101(02)00007-2","article-title":"Interactions between opioid and chemokine receptors: Heterologous desensitization","volume":"13","author":"Steele","year":"2002","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s13365-022-01090-3","article-title":"The synthetic opioid fentanyl increases HIV replication and chemokine co-receptor expression in vitro","volume":"28","author":"Kong","year":"2022","journal-title":"J. NeuroVirology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.virol.2022.10.004","article-title":"Fentanyl enhances HIV infection in vitro","volume":"577","author":"Yan","year":"2022","journal-title":"Virology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/sji.12538","article-title":"Fentanyl Suppresses the Survival of CD4+ T Cells Isolated from Human Umbilical Cord Blood through Inhibition of IKK s-mediated NF-\u03baB Activation","volume":"85","author":"Ma","year":"2017","journal-title":"Scand. J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12977-016-0323-4","article-title":"Are T cells the only HIV-1 reservoir?","volume":"13","author":"Kandathil","year":"2016","journal-title":"Retrovirology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.3389\/fmicb.2018.03185","article-title":"Potential Application of MicroRNA Profiling to the Diagnosis and Prognosis of HIV-1 Infection","volume":"9","author":"Su","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1126\/science.1136319","article-title":"Suppression of microRNA-silencing pathway by HIV-1 during virus replication","volume":"315","author":"Triboulet","year":"2007","journal-title":"Science."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e1000263","DOI":"10.1371\/journal.ppat.1000263","article-title":"miR-198 Inhibits HIV-1 Gene Expression and Replication in Monocytes and Its Mechanism of Action Appears To Involve Repression of Cyclin T1","volume":"5","author":"Sung","year":"2009","journal-title":"PLOS Pathog."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2012.12.016","article-title":"miR-132 enhances HIV-1 replication","volume":"438","author":"Chiang","year":"2013","journal-title":"Virology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.bbrc.2005.09.183","article-title":"Targets for human encoded microRNAs in HIV genes","volume":"337","author":"Hariharan","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_105","first-page":"967","article-title":"Interaction of drugs of abuse and microRNA with HIV: A brief review","volume":"6","author":"Nair","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/hiv.12470","article-title":"Micro RNA-155 is a biomarker of T-cell activation and immune dysfunction in HIV-1-infected patients","volume":"18","author":"Jin","year":"2017","journal-title":"HIV Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.tibs.2008.08.001","article-title":"The ups and downs of SIRT1","volume":"33","author":"Kwon","year":"2008","journal-title":"Trends Biochem Sci."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Gorro\u00f1o, L.E., Escrib\u00e0, T., Boulanger, N., Guardo, A.C., Leon, A., Bargall\u00f3, M.E., Garc\u00eda, F., Gatell, J.M., Plana, M., and Arnedo, M. (2014). Differential MicroRNA Expression Profile between Stimulated PBMCs from HIV-1 Infected Elite Controllers and Viremic Progressors. PLOS ONE, 9.","DOI":"10.1371\/journal.pone.0106360"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11684","DOI":"10.1093\/nar\/gks912","article-title":"The extent of sequence complementarity correlates with the potency of cellular miRNA-mediated restriction of HIV-1","volume":"40","author":"Houzet","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_110","first-page":"E2676","article-title":"MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and virus production","volume":"111","author":"Chen","year":"2014","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.virol.2015.09.016","article-title":"Two cellular microRNAs, miR-196b and miR-1290, contribute to HIV-1 latency","volume":"486","author":"Wang","year":"2015","journal-title":"Virology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/nm1639","article-title":"Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes","volume":"13","author":"Huang","year":"2007","journal-title":"Nat. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e0155245","DOI":"10.1371\/journal.pone.0155245","article-title":"MicroRNA Profile in CD8+ T-Lymphocytes from HIV-Infected Individuals: Relationship with Antiviral Immune Response and Disease Progression","volume":"11","author":"Guardo","year":"2016","journal-title":"PLOS ONE"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1097\/QAD.0000000000001160","article-title":"Plasma microRNA profiling predicts HIV-associated neurocognitive disorder","volume":"30","author":"Asahchop","year":"2016","journal-title":"Aids"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"28279","DOI":"10.1038\/srep28279","article-title":"Anti-HIV microRNA expression in a novel Indian cohort","volume":"6","author":"Dey","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_116","first-page":"1","article-title":"Sterile alpha motif and histidine\/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes is regulated by miRNA-181a","volume":"12","author":"Raymond","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00705-020-04899-7","article-title":"hsa-miR-191-5p inhibits replication of human immunodeficiency virus type 1 by downregulating the expression of NUP50","volume":"166","author":"Zheng","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.molcel.2009.06.003","article-title":"Cellular MicroRNA and P Bodies Modulate Host-HIV-1 Interactions","volume":"34","author":"Nathans","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1093\/nar\/gkr961","article-title":"Interplay between HIV-1 infection and host microRNAs","volume":"40","author":"Sun","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"srep05915","DOI":"10.1038\/srep05915","article-title":"MicroRNAs differentially present in the plasma of HIV elite controllers reduce HIV infection in vitro","volume":"4","author":"Reynoso","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.gene.2018.04.002","article-title":"mircoRNA-3162-3p is a potential biomarker to identify new infections in HIV-1-infected patients","volume":"662","author":"Huang","year":"2018","journal-title":"Gene"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e00549-12","DOI":"10.1128\/mBio.00549-12","article-title":"Next-Generation Sequencing of Small RNAs from HIV-Infected Cells Identifies Phased microRNA Expression Patterns and Candidate Novel microRNAs Differentially Expressed upon Infection","volume":"4","author":"Chang","year":"2013","journal-title":"Mbio"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e00193-13","DOI":"10.1128\/mBio.00193-13","article-title":"In-Depth Analysis of the Interaction of HIV-1 with Cellular microRNA Biogenesis and Effector Mechanisms","volume":"4","author":"Whisnant","year":"2013","journal-title":"Mbio"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s11010-008-9973-4","article-title":"HIV-1 genome-encoded hiv1-mir-H1 impairs cellular responses to infection","volume":"323","author":"Kaul","year":"2009","journal-title":"Mol. Cell. Biochem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1742-4690-11-23","article-title":"A novel HIV-1-encoded microRNA enhances its viral replication by targeting the TATA box region","volume":"11","author":"Zhang","year":"2014","journal-title":"Retrovirology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1742-4690-1-44","article-title":"HIV-1 nef suppression by virally encoded microRNA","volume":"1","author":"Omoto","year":"2004","journal-title":"Retrovirology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1093\/nar\/gkw167","article-title":"Tat-dependent production of an HIV-1 TAR-encoded miRNA-like small RNA","volume":"44","author":"Harwig","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2334-13-250","article-title":"MicroRNA regulation and its effects on cellular transcriptome in Human Immunodeficiency Virus-1 (HIV-1) infected individuals with distinct viral load and CD4 cell counts","volume":"13","author":"Duskova","year":"2013","journal-title":"BMC Infect. Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/1027\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:53Z","timestamp":1760124053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/1027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":128,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["v15041027"],"URL":"https:\/\/doi.org\/10.3390\/v15041027","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}