{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:43:28Z","timestamp":1790613808665,"version":"4.1.0"},"reference-count":118,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,13]],"date-time":"2019-10-13T00:00:00Z","timestamp":1570924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["11180621"],"award-info":[{"award-number":["11180621"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acquired immunodeficiency syndrome (AIDS) has become one of the most devastating pandemics in recorded history. The main causal agent of AIDS is the human immunodeficiency virus (HIV), which infects various cell types of the immune system that express the CD4 receptor on their surfaces. Today, combined antiretroviral therapy (cART) is the standard treatment for all people with HIV; although it has improved the quality of life of people living with HIV (PLWH), it cannot eliminate the latent reservoir of the virus. Therefore HIV\/AIDS has turned from a fatal disease to a chronic disease requiring lifelong treatment. Despite significant viral load suppression, it has been observed that at least half of patients under cART present HIV-associated neurocognitive disorders (HAND), which have been related to HIV-1 infection and replication in the central nervous system (CNS). Several studies have focused on elucidating the mechanism by which HIV-1 can invade the CNS and how it can generate the effects seen in HAND. This review summarizes the research on HIV-1 and its interaction with the CNS with an emphasis on the generation of HAND, how the virus enters the CNS, the relationship between HIV-1 and cells of the CNS, and the effect of cART on these cells.<\/jats:p>","DOI":"10.3390\/cells8101245","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T03:54:13Z","timestamp":1571025253000},"page":"1245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["New Challenges of HIV-1 Infection: How HIV-1 Attacks and Resides in the Central Nervous System"],"prefix":"10.3390","volume":"8","author":[{"given":"Victoria","family":"Rojas-Celis","sequence":"first","affiliation":[{"name":"Instituto de Ciencias Biomedicas, Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Santiago 8910060, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-2516","authenticated-orcid":false,"given":"Fernando","family":"Valiente-Echeverr\u00eda","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Virology Laboratory, Virology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad of Chile, Santiago 8389100, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Soto-Rifo","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Virology Laboratory, Virology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad of Chile, Santiago 8389100, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2563-9711","authenticated-orcid":false,"given":"Daniela","family":"Toro-Ascuy","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biomedicas, Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Santiago 8910060, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,13]]},"reference":[{"key":"ref_1","unstructured":"(2019, July 20). UNAIDS. Available online: https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0140-6736(02)09411-4","article-title":"Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: A collaborative analysis of prospective studies","volume":"360","author":"Egger","year":"2002","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kamat, A., Misra, V., Cassol, E., Ancuta, P., Yan, Z., Li, C., Morgello, S., and Gabuzda, D. (2012). A plasma biomarker signature of immune activation in HIV patients on antiretroviral therapy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030881"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1055\/s-2006-956759","article-title":"Dementia and neurocognitive disorders due to HIV-1 infection","volume":"27","author":"Ances","year":"2007","journal-title":"Semin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0042-6822(90)90373-Y","article-title":"Functions of the auxiliary gene products of the human immunodeficiency virus type 1","volume":"178","author":"Cullen","year":"1990","journal-title":"Virology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1054-3589(07)55010-6","article-title":"Human immunodeficiency virus type 1 assembly, release, and maturation","volume":"55","author":"Adamson","year":"2007","journal-title":"Adv. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1126\/science.3014648","article-title":"The role of mononuclear phagocytes in HTLV-III\/LAV infection","volume":"233","author":"Gartner","year":"1986","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.3016903","article-title":"Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy","volume":"233","author":"Koenig","year":"1986","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/0092-8674(94)90418-9","article-title":"Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1","volume":"78","author":"Pope","year":"1994","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4111","DOI":"10.4049\/jimmunol.155.8.4111","article-title":"Both a precursor and a mature population of dendritic cells can bind HIV. However, only the mature population that expresses CD80 can pass infection to unstimulated CD4+ T cells","volume":"155","author":"Weissman","year":"1995","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kwong, P.D., Wyatt, R., Robinson, J., Sweet, R.W., Sodroski, J., and Hendrickson, W.A. (1998). Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature, 393.","DOI":"10.2210\/pdb1gc1\/pdb"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/348069a0","article-title":"HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain","volume":"348","author":"Koyanagi","year":"1990","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1023\/A:1021070512287","article-title":"HIV-1 replication","volume":"26","author":"Freed","year":"2001","journal-title":"Somatic Cell Mol. Genet."},{"key":"ref_14","unstructured":"Coffin, J.M., Hughes, S.H., and Varmus, H.E. (1997). Integration. Retroviruses, Cold Spring Harbor Laboratory Press."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1086\/498535","article-title":"Susceptibility to HIV infection--disentangling host genetics and host behavior","volume":"193","author":"Telenti","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0960-9822(00)00380-8","article-title":"Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation","volume":"10","author":"Agace","year":"2000","journal-title":"Curr. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1097\/00002030-199204000-00001","article-title":"Cellular transcription factors involved in the regulation of HIV-1 gene expression","volume":"6","author":"Gaynor","year":"1992","journal-title":"Aids"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1056\/NEJM199101313240506","article-title":"The molecular biology of human immunodeficiency virus type 1 infection","volume":"324","author":"Greene","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1348-0421.2008.00008.x","article-title":"Roles of the interactions between Env and Gag proteins in the HIV-1 replication cycle","volume":"52","author":"Murakami","year":"2008","journal-title":"Microbiol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1212\/01.WNL.0000287431.88658.8b","article-title":"Updated research nosology for HIV-associated neurocognitive disorders","volume":"69","author":"Antinori","year":"2007","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1080\/13550280490521078","article-title":"Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected\/acquired immunodeficiency syndrome (HIV\/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: A combined study of two cohorts","volume":"10","author":"Cysique","year":"2004","journal-title":"J. Neurovirol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1212\/WNL.0000000000000492","article-title":"Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline","volume":"82","author":"Grant","year":"2014","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/ana.410190602","article-title":"The AIDS dementia complex: I. Clinical features","volume":"19","author":"Navia","year":"1986","journal-title":"Ann. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/ana.410190603","article-title":"The AIDS dementia complex: II. Neuropathology","volume":"19","author":"Navia","year":"1986","journal-title":"Ann. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1136\/jnnp.69.3.376","article-title":"Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART)","volume":"69","author":"Maschke","year":"2000","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1001\/archneur.58.3.473","article-title":"Factors associated with incident human immunodeficiency virus-dementia","volume":"58","author":"Stern","year":"2001","journal-title":"Arch. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1093\/ije\/dyu092","article-title":"Cohort profile: Recruitment cohorts in the neuropsychological substudy of the multicenter AIDS cohort study","volume":"44","author":"Becker","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_28","first-page":"812","article-title":"Risk factors for cognitive impairment in HIV-1-infected persons with different risk behaviors","volume":"59","author":"Faranca","year":"2002","journal-title":"Arch. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1212\/WNL.0b013e3181bd10e7","article-title":"Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men","volume":"73","author":"Becker","year":"2009","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1212\/WNL.0000000000001156","article-title":"Absence of neurocognitive effect of hepatitis C infection in HIV-coinfected people","volume":"84","author":"Clifford","year":"2015","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1468-1293.2012.01044.x","article-title":"Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients","volume":"14","author":"Fabbiani","year":"2013","journal-title":"HIV Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1212\/WNL.0b013e3182478d64","article-title":"Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder","volume":"78","author":"McCutchan","year":"2012","journal-title":"Neurology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1176\/appi.ajp.158.5.725","article-title":"Meta-analysis of the relationship between HIV infection and risk for depressive disorders","volume":"158","author":"Ciesla","year":"2001","journal-title":"Am. J. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s13365-012-0141-y","article-title":"Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection","volume":"19","author":"Weber","year":"2013","journal-title":"J. Neurovirol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1017\/S1355617703950016","article-title":"Non-acute (residual) neurocognitive effects of cannabis use: A meta-analytic study","volume":"9","author":"Grant","year":"2003","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.brainres.2006.11.059","article-title":"Chronic cocaine exposure in the SCID mouse model of HIV encephalitis","volume":"1134","author":"Griffin","year":"2007","journal-title":"Brain Res."},{"key":"ref_37","unstructured":"(2019, July 25). NATAP. Available online: http:\/\/www.natap.org\/1998\/forums\/natap_forumsmcarthur.htm."},{"key":"ref_38","first-page":"1015","article-title":"Neuropathogenesis of HIV-1 infection. Outstanding questions","volume":"321","author":"Vitkovic","year":"1998","journal-title":"Compt. Rendus Acad. Sci. III Sci. Vie."},{"key":"ref_39","unstructured":"Gendelman, H.E., Lipton, S., Epstein, L., and Swindells, S. (1998). The neurology of AIDS, Chapman & Hall."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/infdis\/jis326","article-title":"Central nervous system viral invasion and inflammation during acute HIV infection","volume":"206","author":"Valcour","year":"2012","journal-title":"Int. J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"a007120","DOI":"10.1101\/cshperspect.a007120","article-title":"HIV-1-related central nervous system disease: Current issues in pathogenesis, diagnosis, and treatment","volume":"2","author":"Spudich","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.brainres.2011.11.052","article-title":"HIV-1 Tat protein increases the permeability of brain endothelial cells by both inhibiting occludin expression and cleaving occludin via matrix metalloproteinase-9","volume":"1436","author":"Xu","year":"2012","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/jnr.10762","article-title":"HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells","volume":"74","author":"Andras","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/jcbfm.2014.54","article-title":"Differential effects of Tat proteins derived from HIV-1 subtypes B and recombinant CRF02_AG on human brain microvascular endothelial cells: Implications for blood\u2013brain barrier dysfunction","volume":"34","author":"Woollard","year":"2014","journal-title":"J. Cerebr. Blood F. Met."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1128\/JVI.75.10.4681-4691.2001","article-title":"Transport of human immunodeficiency virus type 1 pseudoviruses across the blood\u2013brain barrier: Role of envelope proteins and adsorptive endocytosis","volume":"75","author":"Banks","year":"2001","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1097\/00005072-199605000-00003","article-title":"Expression of tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) mRNA in adult human astrocytes: Comparison with adult microglia and fetal astrocytes","volume":"55","author":"Lafortune","year":"1996","journal-title":"J. Neuropath. Exp. Neur."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1097\/QAD.0b013e328360e9fb","article-title":"Endothelial activation biomarkers increase after HIV-1 acquisition: Plasma vascular cell adhesion molecule-1 predicts disease progression","volume":"27","author":"Graham","year":"2013","journal-title":"Aids"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.4049\/jimmunol.158.7.3499","article-title":"A model for monocyte migration through the blood\u2013brain barrier during HIV-1 encephalitis","volume":"158","author":"Persidsky","year":"1997","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1084\/jem.20042413","article-title":"Myeloid and plasmacytoid dendritic cells transfer HIV-1 preferentially to antigen-specific CD4+ T cells","volume":"201","author":"Lore","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1128\/JVI.01844-08","article-title":"Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections","volume":"83","author":"Stacey","year":"2009","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1742-4690-3-28","article-title":"HIV-1 associated dementia: Symptoms and causes","volume":"3","author":"Ghafouri","year":"2006","journal-title":"Retrovirology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S0140-6736(00)60571-8","article-title":"The microglia","volume":"233","year":"1939","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jnr.20093","article-title":"Microglia and Alzheimer\u2019s disease pathogenesis","volume":"77","author":"Streit","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1093\/brain\/awm044","article-title":"Microglial activation in presymptomatic Huntington\u2019s disease gene carriers","volume":"130","author":"Tai","year":"2007","journal-title":"Brain"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.pneurobio.2009.08.001","article-title":"The influence of microglia on the pathogenesis of Parkinson\u2019s disease","volume":"89","author":"Sullivan","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.nurt.2010.05.014","article-title":"Microglial activation and chronic neurodegeneration","volume":"7","author":"Lull","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/385645a0","article-title":"CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia","volume":"385","author":"He","year":"1997","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1128\/JVI.73.1.205-213.1999","article-title":"Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates","volume":"73","author":"Albright","year":"1999","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1189\/jlb.0503204","article-title":"The contribution of monocyte infection and trafficking to viral persistence, and maintenance of the viral reservoir in HIV infection","volume":"74","author":"Crowe","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.3390\/v6041837","article-title":"HIV-1 latency in monocytes\/macrophages","volume":"6","author":"Kumar","year":"2014","journal-title":"Viruses"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1007\/s11481-013-9478-0","article-title":"Apolipoprotein E-dependent differences in innate immune responses of maturing human neuroepithelial progenitor cells exposed to HIV-1","volume":"8","author":"Geffin","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.1365-2990.1995.tb01053.x","article-title":"Neuronal apoptosis in HIV infection in adults","volume":"21","author":"Levy","year":"1995","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-5728(96)00160-9","article-title":"Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase\/polymerase chain reaction in situ hybridization and immunohistochemistry","volume":"74","author":"Wesselingh","year":"1997","journal-title":"J. Neuroimmunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/glia.23081","article-title":"Fate of microglia during HIV-1 infection: From activation to senescence?","volume":"65","author":"Chen","year":"2017","journal-title":"Glia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1523\/JNEUROSCI.3045-16.2017","article-title":"HIV-1 Tat primes and activates microglial NLRP3 inflammasome-mediated neuroinflammation","volume":"37","author":"Chivero","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_66","first-page":"124","article-title":"Microglial cell dysregulation in brain aging and neurodegeneration","volume":"7","author":"Eugenin","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s13365-015-0371-x","article-title":"Blood brain barrier impairment is associated with cerebrospinal fluid markers of neuronal damage in HIV-positive patients","volume":"22","author":"Calcagno","year":"2016","journal-title":"J. Neurovirol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1128\/JVI.02022-14","article-title":"HIV-1 and morphine regulation of autophagy in microglia: Limited interactions in the context of HIV-1 infection and opioid abuse","volume":"89","author":"Rodriguez","year":"2015","journal-title":"J. Virol."},{"key":"ref_69","first-page":"S53","article-title":"Characterization of cultured microglia that can be infected by HIV-1","volume":"6","author":"Albright","year":"2000","journal-title":"J. Neurovirol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s13365-016-0499-3","article-title":"Immortalization of primary microglia: A new platform to study HIV regulation in the central nervous system","volume":"23","author":"Jay","year":"2017","journal-title":"J. Neurovirol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/CS20060043","article-title":"(Peri)vascular production and action of pro-inflammatory cytokines in brain pathology","volume":"112","author":"Konsman","year":"2007","journal-title":"Clin. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12977-015-0141-0","article-title":"HIV-1 non-macrophage-tropic R5 envelope glycoproteins are not more tropic for entry into primary CD4+ T-cells than envelopes highly adapted for macrophages","volume":"12","author":"Musich","year":"2015","journal-title":"Retrovirology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.tube.2015.11.006","article-title":"Mycobacterium tuberculosis EsxO (Rv2346c) promotes bacillary survival by inducing oxidative stress mediated genomic instability in macrophages","volume":"96","author":"Mohanty","year":"2016","journal-title":"Tuberculosis"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jneuroim.2008.06.015","article-title":"HIV-1-infected and\/or immune-activated macrophages regulate astrocyte CXCL8 production through IL-1beta and TNF-alpha: Involvement of mitogen-activated protein kinases and protein kinase R","volume":"200","author":"Zheng","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"10656","DOI":"10.1128\/JVI.01495-15","article-title":"Induction of heme oxygenase-1 deficiency and associated glutamate-mediated neurotoxicity is a highly conserved HIV phenotype of chronic macrophage infection that is resistant to antiretroviral therapy","volume":"89","author":"Gill","year":"2015","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e1171","DOI":"10.1016\/j.cell.2015.08.029","article-title":"SnapShot: Astrocytes in health and disease","volume":"162","author":"Liddelow","year":"2015","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/ana.21697","article-title":"Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia","volume":"66","author":"Churchill","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.celrep.2017.01.027","article-title":"Astrocytes resist HIV-1 fusion but engulf infected macrophage material","volume":"18","author":"Russell","year":"2017","journal-title":"Cell Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1128\/JVI.80.1.541-544.2006","article-title":"Gamma interferon primes productive human immunodeficiency virus infection in astrocytes","volume":"80","year":"2006","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1097\/COH.0b013e32835fc601","article-title":"Where does HIV hide? A focus on the central nervous system","volume":"8","author":"Churchill","year":"2013","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1128\/JVI.03333-13","article-title":"Epigenetic regulation of HIV-1 latency in astrocytes","volume":"88","author":"Narasipura","year":"2014","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nri1527","article-title":"The neuropathogenesis of AIDS","volume":"5","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0006-8993(00)02725-6","article-title":"Neurotoxicity of HIV-1 proteins gp120 and Tat in the rat striatum","volume":"879","author":"Bansal","year":"2000","journal-title":"Brain Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S1044-7431(03)00171-4","article-title":"HIV-1 Tat protein upregulates inflammatory mediators and induces monocyte invasion into the brain","volume":"24","author":"Pu","year":"2003","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3109\/13550289909021993","article-title":"Replication of different clones of human immunodeficiency virus type 1 in primary fetal human astrocytes: Enhancement of viral gene expression by Nef","volume":"5","author":"Bencheikh","year":"1999","journal-title":"J. Neurovirol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Eugenin, E.A., Clements, J.E., Zink, M.C., and Berman, J.W. (2011). Human immunodeficiency virus infection of human astrocytes disrupts blood\u2013brain barrier integrity by a gap junction-dependent mechanism. J. Neurosci.","DOI":"10.1523\/JNEUROSCI.1460-11.2011"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s11481-018-9779-4","article-title":"Exosomal miR-9 released from HIV Tat stimulated astrocytes mediates microglial migration","volume":"13","author":"Yang","year":"2018","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/viro.1996.0108","article-title":"HIV-1 infection of cultured human adult oligodendrocytes","volume":"217","author":"Albright","year":"1996","journal-title":"Virology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/(SICI)1097-4547(19971215)50:6<946::AID-JNR5>3.0.CO;2-D","article-title":"HIV-gp120 affects the functional activity of oligodendrocytes and their susceptibility to complement","volume":"50","author":"Bernardo","year":"1997","journal-title":"J. Neurosci. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/glia.20746","article-title":"HIV-1 Tat and morphine have interactive effects on oligodendrocyte survival and morphology","volume":"57","author":"Hauser","year":"2009","journal-title":"Glia"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"11384","DOI":"10.1523\/JNEUROSCI.4740-14.2015","article-title":"Oligodendrocytes are targets of HIV-1 Tat: NMDA and AMPA receptor-mediated effects on survival and development","volume":"35","author":"Zou","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/jnc.14668","article-title":"Effects of HIV-1 Tat on oligodendrocyte viability are mediated by CaMKIIbeta-GSK3beta interactions","volume":"149","author":"Zou","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1385\/JMN:27:1:079","article-title":"HIV-1 infection of neurons might account for progressive HIV-1-associated encephalopathy in children","volume":"27","author":"Alvarez","year":"2005","journal-title":"J. Mol. Neurosci."},{"key":"ref_95","first-page":"1341","article-title":"Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection","volume":"151","author":"Rottman","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1097\/00002030-199809000-00009","article-title":"Chemokines and receptors in HIV encephalitis","volume":"12","author":"Sanders","year":"1998","journal-title":"Aids"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1084\/jem.165.4.1230","article-title":"The cellular receptor (CD4) of the human immunodeficiency virus is expressed on neurons and glial cells in human brain","volume":"165","author":"Funke","year":"1987","journal-title":"J. Exp. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/intimm\/6.3.377","article-title":"CD4 expression in neurons of the central nervous system","volume":"6","author":"Omri","year":"1994","journal-title":"Int. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1523\/JNEUROSCI.3207-14.2015","article-title":"HIV-1 Tat alters neuronal autophagy by modulating autophagosome fusion to the lysosome: Implications for HIV-associated neurocognitive disorders","volume":"35","author":"Fields","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1083\/jcb.200903070","article-title":"Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages","volume":"186","author":"Kyei","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fnins.2019.00044","article-title":"Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis","volume":"13","author":"Dong","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.immuni.2012.08.010","article-title":"Redefining the viral reservoirs that prevent HIV-1 eradication","volume":"37","author":"Eisele","year":"2012","journal-title":"Immunity"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nm880","article-title":"Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4(+) T cells","volume":"9","author":"Siliciano","year":"2003","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12929-016-0247-2","article-title":"CD44-mediated monocyte transmigration across Cryptococcus neoformans-infected brain microvascular endothelial cells is enhanced by HIV-1 gp41-I90 ectodomain","volume":"23","author":"He","year":"2016","journal-title":"J. Biomed. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3109\/13550289909021297","article-title":"Role of HIV-1 Tat and CC chemokine MIP-1alpha in the pathogenesis of HIV associated central nervous system disorders","volume":"5","author":"Bonwetsch","year":"1999","journal-title":"J. Neurovirol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Christo, P.P., Greco, D.B., Aleixo, A.W., and Livramento, J.A. (2007). Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in patients with and without opportunistic neurological disease during the HAART era. BMC Infect. Dis., 7.","DOI":"10.1186\/1471-2334-7-147"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrmicro.2015.5","article-title":"HIV reservoirs: What, where and how to target them","volume":"14","author":"Churchill","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1212\/01.wnl.0000225183.74521.72","article-title":"Antiretroviral therapy improves cognitive impairment in HIV+ individuals in sub-Saharan Africa","volume":"67","author":"Sacktor","year":"2006","journal-title":"Neurology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1056\/NEJM199803263381301","article-title":"Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators","volume":"338","author":"Palella","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1212\/WNL.0b013e318200d727","article-title":"HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: Charter study","volume":"75","author":"Heaton","year":"2010","journal-title":"Neurology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1097\/QAD.0000000000000538","article-title":"Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease?","volume":"29","author":"Underwood","year":"2015","journal-title":"Aids"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"714","DOI":"10.7326\/0003-4819-143-10-200511150-00008","article-title":"Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals","volume":"143","author":"Clifford","year":"2005","journal-title":"Ann. Intern. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12977-017-0370-5","article-title":"Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain","volume":"14","author":"Asahchop","year":"2017","journal-title":"Retrovirology"},{"key":"ref_114","first-page":"884","article-title":"Brain dysfunction in the era of combination antiretroviral therapy: Implications for the treatment of the aging population of HIV-infected individuals","volume":"11","author":"Clark","year":"2010","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12974-017-0829-2","article-title":"Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity","volume":"14","author":"Ambrosius","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"10683","DOI":"10.1523\/JNEUROSCI.1287-16.2016","article-title":"Insulin treatment prevents neuroinflammation and neuronal injury with restored neurobehavioral function in models of HIV\/AIDS neurodegeneration","volume":"36","author":"Mamik","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.1016\/j.neuron.2017.03.042","article-title":"iPSC-derived human microglia-like cells to study neurological diseases","volume":"94","author":"Abud","year":"2017","journal-title":"Neuron"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.stemcr.2017.06.018","article-title":"An efficient platform for astrocyte differentiation from human induced pluripotent stem cells","volume":"9","author":"Tcw","year":"2017","journal-title":"Stem Cell Rep."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/10\/1245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:25:50Z","timestamp":1760189150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/10\/1245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,13]]},"references-count":118,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["cells8101245"],"URL":"https:\/\/doi.org\/10.3390\/cells8101245","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,13]]}}}