{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:43:20Z","timestamp":1790801000995,"version":"4.1.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01 MH087332"],"award-info":[{"award-number":["R01 MH087332"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01 MH104131"],"award-info":[{"award-number":["R01 MH104131"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01 MH105330"],"award-info":[{"award-number":["R01 MH105330"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["P50 DA026306 (P5)"],"award-info":[{"award-number":["P50 DA026306 (P5)"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>HIV-1 infection remains a major public health concern despite effective combination antiretroviral therapy (cART). The virus enters the central nervous system (CNS) early in infection and continues to cause HIV-associated neurocognitive disorders (HAND). The pathogenic mechanisms of HIV-associated brain injury remain incompletely understood. Since HIV-1 activates the type I interferon system, which signals via interferon-\u03b1 receptor (IFNAR) 1 and 2, this study investigated the potential role of IFNAR1 in HIV-induced neurotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We cross-bred HIVgp120-transgenic (tg) and IFNAR1 knockout (IFNAR1KO) mice. At 11\u201314 months of age, we performed a behavioral assessment and subsequently analyzed neuropathological alterations using deconvolution and quantitative immunofluorescence microscopy, quantitative RT-PCR, and bioinformatics. Western blotting of brain lysates and an in vitro neurotoxicity assay were employed for analysis of cellular signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that IFNAR1KO results in partial, sex-dependent protection from neuronal injury and behavioral deficits in a transgenic model of HIV-induced brain injury. The IFNAR1KO rescues spatial memory and ameliorates loss of presynaptic terminals preferentially in female HIVgp120tg mice. Similarly, expression of genes involved in neurotransmission reveals sex-dependent effects of IFNAR1KO and HIVgp120. In contrast, IFNAR1-deficiency, independent of sex, limits damage to neuronal dendrites, microgliosis, and activation of p38 MAPK and restores ERK activity in the HIVgp120tg brain. In vitro, inhibition of p38 MAPK abrogates neurotoxicity caused similarly by blockade of ERK kinase and HIVgp120.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that IFNAR1 plays a pivotal role in both sex-dependent and independent processes of neuronal injury and behavioral impairment triggered by HIV-1.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-020-01894-2","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T11:03:53Z","timestamp":1596020633000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A pivotal role for Interferon-\u03b1 receptor-1 in neuronal injury induced by HIV-1"],"prefix":"10.1186","volume":"17","author":[{"given":"Hina","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ojeda-Ju\u00e1rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky","family":"Maung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-670X","authenticated-orcid":false,"given":"Marcus","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"1894_CR1","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1212\/WNL.0b013e318200d727","volume":"75","author":"RK Heaton","year":"2010","unstructured":"Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75:2087\u201396.","journal-title":"Neurology"},{"key":"1894_CR2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s13365-010-0006-1","volume":"17","author":"RK Heaton","year":"2011","unstructured":"Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011;17:3\u201316.","journal-title":"J Neurovirol"},{"key":"1894_CR3","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/COH.0000000000000110","volume":"9","author":"RB Meeker","year":"2014","unstructured":"Meeker RB, Asahchop E, Power C. The brain and HAART: collaborative and combative connections. Curr Opin HIV AIDS. 2014;9:579\u201384.","journal-title":"Curr Opin HIV AIDS"},{"key":"1894_CR4","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1001\/archneur.1997.00550160054016","volume":"54","author":"RJ Ellis","year":"1997","unstructured":"Ellis RJ, Deutsch R, Heaton RK, Marcotte TD, McCutchan JA, Nelson JA, Abramson I, Thal LJ, Atkinson JH, Wallace MR, Grant I. Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group. Arch Neurol. 1997;54:416\u201324.","journal-title":"Arch Neurol"},{"key":"1894_CR5","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/ana.22053","volume":"67","author":"JC McArthur","year":"2010","unstructured":"McArthur JC, Steiner J, Sacktor N, Nath A. Human immunodeficiency virus-associated neurocognitive disorders: mind the gap. Ann Neurol. 2010;67:699\u2013714.","journal-title":"Ann Neurol"},{"key":"1894_CR6","doi-asserted-by":"crossref","unstructured":"Sanchez AB, Kaul M. Neuronal stress and injury caused by HIV-1, cART and drug abuse: converging contributions to HAND. Brain Sci. 2017;7.","DOI":"10.3390\/brainsci7030025"},{"key":"1894_CR7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1089\/vim.2018.0085","volume":"32","author":"VE Thaney","year":"2019","unstructured":"Thaney VE, Kaul M. Type I interferons in NeuroHIV. Viral Immunol. 2019;32:7\u201314.","journal-title":"Viral Immunol"},{"key":"1894_CR8","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/35073667","volume":"410","author":"M Kaul","year":"2001","unstructured":"Kaul M, Garden GA, Lipton SA. Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature. 2001;410:988\u201394.","journal-title":"Nature"},{"key":"1894_CR9","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1126\/science.287.5453.602","volume":"287","author":"S Gartner","year":"2000","unstructured":"Gartner S. HIV infection and dementia. Science. 2000;287:602\u20134.","journal-title":"Science"},{"key":"1894_CR10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nri1527","volume":"5","author":"F Gonzalez-Scarano","year":"2005","unstructured":"Gonzalez-Scarano F, Martin-Garcia J. The neuropathogenesis of AIDS. Nat Rev Immunol. 2005;5:69\u201381.","journal-title":"Nat Rev Immunol"},{"key":"1894_CR11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s11481-010-9205-z","volume":"5","author":"KA Lindl","year":"2010","unstructured":"Lindl KA, Marks DR, Kolson DL, Jordan-Sciutto KL. HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities. J Neuroimmune Pharmacol. 2010;5:294\u2013309.","journal-title":"J Neuroimmune Pharmacol"},{"key":"1894_CR12","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1365-2559.2004.02004.x","volume":"45","author":"JE Bell","year":"2004","unstructured":"Bell JE. An update on the neuropathology of HIV in the HAART era. Histopathology. 2004;45:549\u201359.","journal-title":"Histopathology"},{"issue":"Suppl 1","key":"1894_CR13","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/sj.cdd.4401623","volume":"12","author":"M Kaul","year":"2005","unstructured":"Kaul M, Zheng J, Okamoto S, Gendelman HE, Lipton SA. HIV-1 infection and AIDS: consequences for the central nervous system. Cell Death Differ. 2005;12(Suppl 1):878\u201392.","journal-title":"Cell Death Differ"},{"key":"1894_CR14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrn2040","volume":"8","author":"R Ellis","year":"2007","unstructured":"Ellis R, Langford D, Masliah E. HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci. 2007;8:33\u201344.","journal-title":"Nat Rev Neurosci"},{"key":"1894_CR15","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.4049\/jimmunol.1302915","volume":"193","author":"R Maung","year":"2014","unstructured":"Maung R, Hoefer MM, Sanchez AB, Sejbuk NE, Medders KE, Desai MK, Catalan IC, Dowling CC, de Rozieres CM, Garden GA, et al. CCR5 knockout prevents neuronal injury and behavioral impairment induced in a transgenic mouse model by a CXCR4-using HIV-1 glycoprotein 120. J Immunol. 2014;193:1895\u2013910.","journal-title":"J Immunol"},{"key":"1894_CR16","doi-asserted-by":"crossref","first-page":"46514","DOI":"10.1038\/srep46514","volume":"7","author":"VE Thaney","year":"2017","unstructured":"Thaney VE, O'Neill AM, Hoefer MM, Maung R, Sanchez AB, Kaul M. IFNbeta protects neurons from damage in a murine model of HIV-1 associated brain injury. Sci Rep. 2017;7:46514.","journal-title":"Sci Rep"},{"key":"1894_CR17","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s12974-016-0724-2","volume":"13","author":"AB Sanchez","year":"2016","unstructured":"Sanchez AB, Medders KE, Maung R, Sanchez-Pavon P, Ojeda-Juarez D, Kaul M. CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca(2+) channels upstream of p38 MAPK. J Neuroinflammation. 2016;13:252.","journal-title":"J Neuroinflammation"},{"key":"1894_CR18","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.expneurol.2014.09.010","volume":"263","author":"MM Hoefer","year":"2015","unstructured":"Hoefer MM, Sanchez AB, Maung R, de Rozieres CM, Catalan IC, Dowling CC, Thaney VE, Pina-Crespo J, Zhang D, Roberts AJ, Kaul M. Combination of methamphetamine and HIV-1 gp120 causes distinct long-term alterations of behavior, gene expression, and injury in the central nervous system. Exp Neurol. 2015;263:221\u201334.","journal-title":"Exp Neurol"},{"key":"1894_CR19","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/367188a0","volume":"367","author":"SM Toggas","year":"1994","unstructured":"Toggas SM, Masliah E, Rockenstein EM, Rall GF, Abraham CR, Mucke L. Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature. 1994;367:188\u201393.","journal-title":"Nature"},{"key":"1894_CR20","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.1046\/j.1460-9568.1999.00857.x","volume":"11","author":"R D'Hooge","year":"1999","unstructured":"D'Hooge R, Franck F, Mucke L, De Deyn PP. Age-related behavioural deficits in transgenic mice expressing the HIV-1 coat protein gp120. Eur J Neurosci. 1999;11:4398\u2013402.","journal-title":"Eur J Neurosci"},{"key":"1894_CR21","doi-asserted-by":"crossref","unstructured":"De Andrea M, Ravera R, Gioia D, Gariglio M, Landolfo S: The interferon system: an overview. Eur J Paediatr Neurol 2002, 6 Suppl A:A41-46; discussion A55-48.","DOI":"10.1053\/ejpn.2002.0573"},{"key":"1894_CR22","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.molimm.2004.06.018","volume":"42","author":"C Speth","year":"2005","unstructured":"Speth C, Dierich MP, Sopper S. HIV-infection of the central nervous system: the tightrope walk of innate immunity. Mol Immunol. 2005;42:213\u201328.","journal-title":"Mol Immunol"},{"key":"1894_CR23","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nri1105","volume":"3","author":"DE Griffin","year":"2003","unstructured":"Griffin DE. Immune responses to RNA-virus infections of the CNS. Nat Rev Immunol. 2003;3:493\u2013502.","journal-title":"Nat Rev Immunol"},{"key":"1894_CR24","doi-asserted-by":"crossref","first-page":"20053","DOI":"10.1074\/jbc.R700006200","volume":"282","author":"NA de Weerd","year":"2007","unstructured":"de Weerd NA, Samarajiwa SA, Hertzog PJ. Type I interferon receptors: biochemistry and biological functions. J Biol Chem. 2007;282:20053\u20137.","journal-title":"J Biol Chem"},{"key":"1894_CR25","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nrmicro3449","volume":"13","author":"T Doyle","year":"2015","unstructured":"Doyle T, Goujon C, Malim MH. HIV-1 and interferons: who\u2019s interfering with whom? Nat Rev Microbiol. 2015;13:403\u201313.","journal-title":"Nat Rev Microbiol"},{"key":"1894_CR26","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature09907","volume":"472","author":"JW Schoggins","year":"2011","unstructured":"Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011;472:481\u20135.","journal-title":"Nature"},{"issue":"Suppl 1","key":"1894_CR27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/753312747","volume":"10","author":"SA Barber","year":"2004","unstructured":"Barber SA, Herbst DS, Bullock BT, Gama L, Clements JE. Innate immune responses and control of acute simian immunodeficiency virus replication in the central nervous system. J Neurovirol. 2004;10(Suppl 1):15\u201320.","journal-title":"J Neurovirol"},{"key":"1894_CR28","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1097\/QAD.0b013e3282f08c2f","volume":"21","author":"AR Sas","year":"2007","unstructured":"Sas AR, Bimonte-Nelson HA, Tyor WR. Cognitive dysfunction in HIV encephalitic SCID mice correlates with levels of Interferon-alpha in the brain. AIDS. 2007;21:2151\u20139.","journal-title":"AIDS"},{"key":"1894_CR29","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0165-5728(00)00315-5","volume":"110","author":"R Kitai","year":"2000","unstructured":"Kitai R, Zhao ML, Zhang N, Hua LL, Lee SC. Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta. J Neuroimmunol. 2000;110:230\u20139.","journal-title":"J Neuroimmunol"},{"key":"1894_CR30","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.1523\/JNEUROSCI.5595-08.2009","volume":"29","author":"AR Sas","year":"2009","unstructured":"Sas AR, Bimonte-Nelson H, Smothers CT, Woodward J, Tyor WR. Interferon-alpha causes neuronal dysfunction in encephalitis. J Neurosci. 2009;29:3948\u201355.","journal-title":"J Neurosci"},{"key":"1894_CR31","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1126\/science.8009221","volume":"264","author":"U Muller","year":"1994","unstructured":"Muller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, Zinkernagel RM, Aguet M. Functional role of type I and type II interferons in antiviral defense. Science. 1994;264:1918\u201321.","journal-title":"Science"},{"key":"1894_CR32","doi-asserted-by":"crossref","first-page":"8212","DOI":"10.1073\/pnas.96.14.8212","volume":"96","author":"M Kaul","year":"1999","unstructured":"Kaul M, Lipton SA. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc Natl Acad Sci U S A. 1999;96:8212\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1894_CR33","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/sj.cdd.4402006","volume":"14","author":"M Kaul","year":"2007","unstructured":"Kaul M, Ma Q, Medders KE, Desai MK, Lipton SA. HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death Differ. 2007;14:296\u2013305.","journal-title":"Cell Death Differ"},{"key":"1894_CR34","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.4049\/jimmunol.0902535","volume":"185","author":"KE Medders","year":"2010","unstructured":"Medders KE, Sejbuk NE, Maung R, Desai MK, Kaul M. Activation of p38 MAPK is required in monocytic and neuronal cells for HIV glycoprotein 120-induced neurotoxicity. J Immunol. 2010;185:4883\u201395.","journal-title":"J Immunol"},{"key":"1894_CR35","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/hipo.20122","volume":"15","author":"DG Mumby","year":"2005","unstructured":"Mumby DG, Tremblay A, Lecluse V, Lehmann H. Hippocampal damage and anterograde object-recognition in rats after long retention intervals. Hippocampus. 2005;15:1050\u20136.","journal-title":"Hippocampus"},{"key":"1894_CR36","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1523\/JNEUROSCI.1346-04.2004","volume":"24","author":"BD Winters","year":"2004","unstructured":"Winters BD, Forwood SE, Cowell RA, Saksida LM, Bussey TJ. Double dissociation between the effects of peri-postrhinal cortex and hippocampal lesions on tests of object recognition and spatial memory: heterogeneity of function within the temporal lobe. J Neurosci. 2004;24:5901\u20138.","journal-title":"J Neurosci"},{"key":"1894_CR37","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbr.2005.11.003","volume":"168","author":"CK Lieben","year":"2006","unstructured":"Lieben CK, Steinbusch HW, Blokland A. 5,7-DHT lesion of the dorsal raphe nuclei impairs object recognition but not affective behavior and corticosterone response to stressor in the rat. Behav Brain Res. 2006;168:197\u2013207.","journal-title":"Behav Brain Res"},{"key":"1894_CR38","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402\u20138.","journal-title":"Methods"},{"key":"1894_CR39","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1128\/AAC.01632-15","volume":"60","author":"AB Sanchez","year":"2016","unstructured":"Sanchez AB, Varano GP, de Rozieres CM, Maung R, Catalan IC, Dowling CC, Sejbuk NE, Hoefer MM, Kaul M. Antiretrovirals, methamphetamine, and HIV-1 envelope protein gp120 compromise neuronal energy homeostasis in association with various degrees of synaptic and neuritic damage. Antimicrob Agents Chemother. 2016;60:168\u201379.","journal-title":"Antimicrob Agents Chemother"},{"key":"1894_CR40","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/382829a0","volume":"382","author":"CC Bleul","year":"1996","unstructured":"Bleul CC, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, Springer TA. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR\/fusin and blocks HIV-1 entry. Nature. 1996;382:829\u201333.","journal-title":"Nature"},{"key":"1894_CR41","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/381667a0","volume":"381","author":"T Dragic","year":"1996","unstructured":"Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996;381:667\u201373.","journal-title":"Nature"},{"key":"1894_CR42","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.biochi.2007.04.015","volume":"89","author":"O Haller","year":"2007","unstructured":"Haller O, Staeheli P, Kochs G. Interferon-induced Mx proteins in antiviral host defense. Biochimie. 2007;89:812\u20138.","journal-title":"Biochimie"},{"key":"1894_CR43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1615\/CritRevNeurobiol.v16.i12.50","volume":"16","author":"I Mocchetti","year":"2004","unstructured":"Mocchetti I, Bachis A. Brain-derived neurotrophic factor activation of TrkB protects neurons from HIV-1\/gp120-induced cell death. Crit Rev Neurobiol. 2004;16:51\u20137.","journal-title":"Crit Rev Neurobiol"},{"key":"1894_CR44","doi-asserted-by":"crossref","unstructured":"Koga Y, Tsurumaki H, Aoki-Saito H, Sato M, Yatomi M, Takehara K, Hisada T. Roles of cyclic AMP response element binding activation in the ERK1\/2 and p38 MAPK signalling pathway in central nervous system, cardiovascular system, osteoclast differentiation and mucin and cytokine production. Int J Mol Sci. 2019;20.","DOI":"10.3390\/ijms20061346"},{"key":"1894_CR45","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","volume":"30","author":"A Kramer","year":"2014","unstructured":"Kramer A, Green J, Pollard J Jr, Tugendreich S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 2014;30:523\u201330.","journal-title":"Bioinformatics"},{"key":"1894_CR46","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1212\/01.WNL.0000287431.88658.8b","volume":"69","author":"A Antinori","year":"2007","unstructured":"Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69:1789\u201399.","journal-title":"Neurology"},{"key":"1894_CR47","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrneurol.2016.27","volume":"12","author":"D Saylor","year":"2016","unstructured":"Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M, Mankowski JL, Brown A, Volsky DJ, McArthur JC. HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat Rev Neurol. 2016;12:234\u201348.","journal-title":"Nat Rev Neurol"},{"key":"1894_CR48","doi-asserted-by":"crossref","first-page":"9254","DOI":"10.1128\/JVI.00854-10","volume":"84","author":"C Goujon","year":"2010","unstructured":"Goujon C, Malim MH. Characterization of the alpha interferon-induced postentry block to HIV-1 infection in primary human macrophages and T cells. J Virol. 2010;84:9254\u201366.","journal-title":"J Virol"},{"key":"1894_CR49","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1006\/viro.1993.1110","volume":"193","author":"PR Meylan","year":"1993","unstructured":"Meylan PR, Guatelli JC, Munis JR, Richman DD, Kornbluth RS. Mechanisms for the inhibition of HIV replication by interferons-alpha, -beta, and -gamma in primary human macrophages. Virology. 1993;193:138\u201348.","journal-title":"Virology"},{"key":"1894_CR50","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1128\/jvi.66.3.1321-1328.1992","volume":"66","author":"Y Shirazi","year":"1992","unstructured":"Shirazi Y, Pitha PM. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle. J Virol. 1992;66:1321\u20138.","journal-title":"J Virol"},{"key":"1894_CR51","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1128\/CMR.14.4.778-809.2001","volume":"14","author":"CE Samuel","year":"2001","unstructured":"Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14:778\u2013809.","journal-title":"Clin Microbiol Rev"},{"key":"1894_CR52","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1212\/WNL.45.5.947","volume":"45","author":"MA Pavol","year":"1995","unstructured":"Pavol MA, Meyers CA, Rexer JL, Valentine AD, Mattis PJ, Talpaz M. Pattern of neurobehavioral deficits associated with interferon alfa therapy for leukemia. Neurology. 1995;45:947\u201350.","journal-title":"Neurology"},{"key":"1894_CR53","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jad.2004.09.004","volume":"84","author":"P Amodio","year":"2005","unstructured":"Amodio P, De Toni EN, Cavalletto L, Mapelli D, Bernardinello E, Del Piccolo F, Bergamelli C, Costanzo R, Bergamaschi F, Poma SZ, et al. Mood, cognition and EEG changes during interferon alpha (alpha-IFN) treatment for chronic hepatitis C. J Affect Disord. 2005;84:93\u20138.","journal-title":"J Affect Disord"},{"key":"1894_CR54","first-page":"39","volume":"25","author":"AD Valentine","year":"1998","unstructured":"Valentine AD, Meyers CA, Kling MA, Richelson E, Hauser P. Mood and cognitive side effects of interferon-alpha therapy. Semin Oncol. 1998;25:39\u201347.","journal-title":"Semin Oncol"},{"key":"1894_CR55","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nrd2422","volume":"6","author":"EC Borden","year":"2007","unstructured":"Borden EC, Sen GC, Uze G, Silverman RH, Ransohoff RM, Foster GR, Stark GR. Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov. 2007;6:975\u201390.","journal-title":"Nat Rev Drug Discov"},{"issue":"Suppl 3","key":"1894_CR56","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1093\/infdis\/jiu175","volume":"209","author":"MM Addo","year":"2014","unstructured":"Addo MM, Altfeld M. Sex-based differences in HIV type 1 pathogenesis. J Infect Dis. 2014;209(Suppl 3):S86\u201392.","journal-title":"J Infect Dis"},{"key":"1894_CR57","doi-asserted-by":"publisher","unstructured":"Rubin LH, Maki PM. Neurocognitive complications of hiv infection in women: insights from the WIHS cohort. Curr Top Behav Neurosci. 2019. https:\/\/doi.org\/10.1007\/7854_2019_101.","DOI":"10.1007\/7854_2019_101"},{"key":"1894_CR58","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3389\/fnbeh.2017.00212","volume":"11","author":"KA McLaurin","year":"2017","unstructured":"McLaurin KA, Booze RM, Mactutus CF, Fairchild AJ. Sex matters: robust sex differences in signal detection in the HIV-1 transgenic rat. Front Behav Neurosci. 2017;11:212.","journal-title":"Front Behav Neurosci"},{"key":"1894_CR59","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0031-9384(01)00515-7","volume":"73","author":"R Paylor","year":"2001","unstructured":"Paylor R, Zhao Y, Libbey M, Westphal H, Crawley JN. Learning impairments and motor dysfunctions in adult Lhx5-deficient mice displaying hippocampal disorganization. Physiol Behav. 2001;73:781\u201392.","journal-title":"Physiol Behav"},{"key":"1894_CR60","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cell.2015.08.069","volume":"163","author":"P Ejlerskov","year":"2015","unstructured":"Ejlerskov P, Hultberg JG, Wang J, Carlsson R, Ambjorn M, Kuss M, Liu Y, Porcu G, Kolkova K, Friis Rundsten C, et al. Lack of neuronal IFN-beta-IFNAR causes lewy body- and Parkinson\u2019s disease-like dementia. Cell. 2015;163:324\u201339.","journal-title":"Cell"},{"key":"1894_CR61","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/ana.22070","volume":"68","author":"YJ Kang","year":"2010","unstructured":"Kang YJ, Digicaylioglu M, Russo R, Kaul M, Achim CL, Fletcher L, Masliah E, Lipton SA. Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disorders. Ann Neurol. 2010;68:342\u201352.","journal-title":"Ann Neurol"},{"key":"1894_CR62","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1177\/026988110001400305","volume":"14","author":"A Nath","year":"2000","unstructured":"Nath A, Anderson C, Jones M, Maragos W, Booze R, Mactutus C, Bell J, Hauser KF, Mattson M. Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia. J Psychopharmacol. 2000;14:222\u20137.","journal-title":"J Psychopharmacol"},{"key":"1894_CR63","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nn835","volume":"5","author":"GE Hardingham","year":"2002","unstructured":"Hardingham GE, Fukunaga Y, Bading H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci. 2002;5:405\u201314.","journal-title":"Nat Neurosci"},{"key":"1894_CR64","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/hipo.22108","volume":"23","author":"S Middei","year":"2013","unstructured":"Middei S, Houeland G, Cavallucci V, Ammassari-Teule M, D'Amelio M, Marie H. CREB is necessary for synaptic maintenance and learning-induced changes of the AMPA receptor GluA1 subunit. Hippocampus. 2013;23:488\u201399.","journal-title":"Hippocampus"},{"key":"1894_CR65","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1007\/s11064-012-0797-y","volume":"37","author":"MW Lopes","year":"2012","unstructured":"Lopes MW, Soares FM, de Mello N, Nunes JC, de Cordova FM, Walz R, Leal RB. Time-dependent modulation of mitogen activated protein kinases and AKT in rat hippocampus and cortex in the pilocarpine model of epilepsy. Neurochem Res. 2012;37:1868\u201378.","journal-title":"Neurochem Res"},{"key":"1894_CR66","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.yfrne.2010.10.001","volume":"32","author":"TC Ngun","year":"2011","unstructured":"Ngun TC, Ghahramani N, Sanchez FJ, Bocklandt S, Vilain E. The genetics of sex differences in brain and behavior. Front Neuroendocrinol. 2011;32:227\u201346.","journal-title":"Front Neuroendocrinol"},{"key":"1894_CR67","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.bbi.2019.04.029","volume":"80","author":"R Putatunda","year":"2019","unstructured":"Putatunda R, Zhang Y, Li F, Fagan PR, Zhao H, Ramirez SH, Pratico D, Barbe MF, Hu W. Sex-specific neurogenic deficits and neurocognitive disorders in middle-aged HIV-1 Tg26 transgenic mice. Brain Behav Immun. 2019;80:488\u201399.","journal-title":"Brain Behav Immun"},{"key":"1894_CR68","doi-asserted-by":"publisher","unstructured":"Ojeda-Juarez D, Shah R, Adam Fields J, Harahap-Carrillo I, Koury J, Maung R, Gelman BB, Baaten BJ, Roberts AJ, Kaul M: Lipocalin-2 mediates HIV-1 induced neuronal injury and behavioral deficits by overriding CCR5-dependent protection. Brain Behav Immun 2020, 11::S0889-1591(0820)30332-30339. doi: https:\/\/doi.org\/10.1016\/j.bbi.2020.06.016. Online ahead of print.","DOI":"10.1016\/j.bbi.2020.06.016"},{"key":"1894_CR69","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s13365-010-0013-2","volume":"17","author":"SL Letendre","year":"2011","unstructured":"Letendre SL, Zheng JC, Kaul M, Yiannoutsos CT, Ellis RJ, Taylor MJ, Marquie-Beck J, Navia B, Consortium HIVN. Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals. J Neurovirol. 2011;17:63\u20139.","journal-title":"J Neurovirol"},{"key":"1894_CR70","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0046178","volume":"7","author":"BB Gelman","year":"2012","unstructured":"Gelman BB, Chen T, Lisinicchia JG, Soukup VM, Carmical JR, Starkey JM, Masliah E, Commins DL, Brandt D, Grant I, et al. The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment. PLoS ONE. 2012;7:e46178.","journal-title":"PLoS ONE"},{"key":"1894_CR71","doi-asserted-by":"crossref","unstructured":"Cheng L, Yu H, Li G, Li F, Ma J, Li J, Chi L, Zhang L, Su L. Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection. JCI Insight. 2017;2.","DOI":"10.1172\/jci.insight.94366"},{"key":"1894_CR72","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1172\/JCI89488","volume":"127","author":"A Zhen","year":"2017","unstructured":"Zhen A, Rezek V, Youn C, Lam B, Chang N, Rick J, Carrillo M, Martin H, Kasparian S, Syed P, et al. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection. J Clin Invest. 2017;127:260\u20138.","journal-title":"J Clin Invest"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01894-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-020-01894-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01894-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T23:54:48Z","timestamp":1723334088000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-01894-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,29]]},"references-count":72,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1894"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-01894-2","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,29]]},"assertion":[{"value":"28 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All procedures involving animals were performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committees of the Sanford-Burnham-Prebys Medical Discovery Institute, The Scripps Research Institute and the University of California, Riverside.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/A","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"226"}}