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HIV infiltrates the central nervous system (CNS) early during primary infection where it establishes persistent infection in microglia (resident macrophages) and astrocytes that in turn release inflammatory cytokines, small neurotoxic mediators, and viral proteins. While the molecular mechanisms underlying pathology in HAND remain poorly understood, synaptodendritic damage has emerged as a hallmark of HIV infection of the CNS. Here, we report that the HIV viral envelope glycoprotein gp120 induces the formation of aberrant, rod-shaped cofilin-actin inclusions (rods) in cultured mouse hippocampal neurons via a signaling pathway common to other neurodegenerative stimuli including oligomeric, soluble amyloid-\u03b2 and proinflammatory cytokines. Previous studies showed that synaptic function is impaired preferentially in the distal proximity of rods within dendrites. Our studies demonstrate gp120 binding to either chemokine co-receptor CCR5 or CXCR4 is capable of inducing rod formation, and signaling through this pathway requires active NADPH oxidase presumably through the formation of superoxide (O<jats:sup>2-<\/jats:sup>) and the expression of cellular prion protein (PrP<jats:sup>C<\/jats:sup>). These findings link gp120-mediated oxidative stress to the generation of rods, which may underlie early synaptic dysfunction observed in HAND.<\/jats:p>","DOI":"10.1371\/journal.pone.0248309","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T18:32:31Z","timestamp":1615487551000},"page":"e0248309","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":29,"title":["Direct interaction of HIV gp120 with neuronal CXCR4 and CCR5 receptors induces cofilin-actin rod pathology via a cellular prion protein- and NOX-dependent mechanism"],"prefix":"10.1371","volume":"16","author":[{"given":"Lisa K.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac W.","family":"Babcock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie 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hippocampal neurons in culture. I. 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Gavriel","year":"2020","journal-title":"J Alzheimers Dis JAD"},{"key":"pone.0248309.ref064","doi-asserted-by":"crossref","first-page":"23631","DOI":"10.18632\/oncotarget.4604","article-title":"A NOX2\/Egr-1\/Fyn pathway delineates new targets for TKI-resistant malignancies","volume":"6","author":"ME Irwin","year":"2015","journal-title":"Oncotarget"},{"key":"pone.0248309.ref065","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jnr.22748","article-title":"Neutral sphingomyelinase activation precedes NADPH oxidase-dependent damage in neurons exposed to the proinflammatory cytokine tumor necrosis factor-alpha","volume":"90","author":"BM Barth","year":"2012","journal-title":"J Neurosci Res"},{"key":"pone.0248309.ref066","doi-asserted-by":"crossref","first-page":"13117","DOI":"10.1523\/JNEUROSCI.3322-07.2007","article-title":"Cdc42 regulates cofilin during the establishment of neuronal polarity","volume":"27","author":"BK Garvalov","year":"2007","journal-title":"J Neurosci Off 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Commun"},{"key":"pone.0248309.ref080","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20225647","article-title":"Oligomerization Affects the Ability of Human Cyclase-Associated Proteins 1 and 2 to Promote Actin Severing by Cofilins","volume":"20","author":"V Purde","year":"2019","journal-title":"Int J Mol Sci"},{"key":"pone.0248309.ref081","doi-asserted-by":"crossref","first-page":"65741","DOI":"10.1155\/JBB\/2006\/65741","article-title":"HIV neurotoxicity: potential therapeutic interventions","volume":"2006","author":"DR Wallace","year":"2006","journal-title":"J Biomed Biotechnol"},{"key":"pone.0248309.ref082","doi-asserted-by":"crossref","first-page":"e70565","DOI":"10.1371\/journal.pone.0070565","article-title":"Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis","volume":"8","author":"L Guo","year":"2013","journal-title":"PLoS One"},{"key":"pone.0248309.ref083","doi-asserted-by":"crossref","first-page":"10550","DOI":"10.1523\/JNEUROSCI.4403-14.2015","article-title":"Induction of Interleukin-1\u03b2 by Human Immunodeficiency Virus-1 Viral Proteins Leads to Increased Levels of Neuronal Ferritin Heavy Chain, Synaptic Injury, and Deficits in Flexible Attention","volume":"35","author":"L Festa","year":"2015","journal-title":"J Neurosci"},{"key":"pone.0248309.ref084","doi-asserted-by":"crossref","first-page":"17215","DOI":"10.1038\/s41598-018-35478-1","article-title":"HIV-1 Envelope Glycoproteins Induce the Production of TNF-\u03b1 and IL-10 in Human Monocytes by Activating Calcium Pathway","volume":"8","author":"R Plan\u00e8s","year":"2018","journal-title":"Sci Rep"},{"key":"pone.0248309.ref085","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1124\/mol.106.025973","article-title":"HIV-1 viral envelope glycoprotein gp120 triggers an inflammatory response in cultured rat astrocytes and regulates the functional expression of P-glycoprotein","volume":"70","author":"PT Ronaldson","year":"2006","journal-title":"Mol Pharmacol"},{"key":"pone.0248309.ref086","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1002\/jnr.22720","article-title":"Regulation of P-glycoprotein by human immunodeficiency virus-1 in primary cultures of human fetal astrocytes","volume":"89","author":"T Ashraf","year":"2011","journal-title":"J Neurosci Res"},{"key":"pone.0248309.ref087","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1742-2094-7-96","article-title":"HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated through the NF-\u03baB pathway and can be silenced by gp120-specific siRNA","volume":"7","author":"A Shah","year":"2010","journal-title":"J Neuroinflammation"},{"key":"pone.0248309.ref088","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/sj.cdd.4402006","article-title":"HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection","volume":"14","author":"M Kaul","year":"2007","journal-title":"Cell Death Differ"},{"key":"pone.0248309.ref089","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/jnen\/60.4.377","article-title":"Hippocampal Injury and Alterations in Neuronal Chemokine Co-Receptor Expression in Patients With AIDS","volume":"60","author":"CK Petito","year":"2001","journal-title":"J Neuropathol Exp Neurol"},{"key":"pone.0248309.ref090","doi-asserted-by":"crossref","first-page":"14500","DOI":"10.1073\/pnas.95.24.14500","article-title":"Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity","volume":"95","author":"O Meucci","year":"1998","journal-title":"Proc Natl Acad Sci"},{"key":"pone.0248309.ref091","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0304-3940(01)02149-8","article-title":"Cellular expression of functional chemokine receptor CCR5 and CXCR4 in human embryonic neurons","volume":"311","author":"A Boutet","year":"2001","journal-title":"Neurosci Lett"},{"key":"pone.0248309.ref092","first-page":"1895","article-title":"CCR5 knockout prevents neuronal injury and behavioral impairment induced in a transgenic mouse model by a CXCR4-using HIV-1 glycoprotein 120","volume":"193","author":"R Maung","year":"2014","journal-title":"J Immunol Baltim Md 1950"},{"key":"pone.0248309.ref093","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/jnc.14015","article-title":"The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of neurotoxicity","volume":"141","author":"V Avdoshina","year":"2017","journal-title":"J Neurochem"},{"key":"pone.0248309.ref094","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13041-019-0482-z","article-title":"Helix-A peptide prevents gp120-mediated neuronal loss","volume":"12","author":"V Avdoshina","year":"2019","journal-title":"Mol Brain"},{"key":"pone.0248309.ref095","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/s41419-019-1920-7","article-title":"Histone deacetylase 6 inhibition rescues axonal transport impairments and prevents the neurotoxicity of HIV-1 envelope protein gp120","volume":"10","author":"ED Wenzel","year":"2019","journal-title":"Cell Death Dis"},{"key":"pone.0248309.ref096","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1742-2094-1-7","article-title":"Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia","volume":"1","author":"S Iskander","year":"2004","journal-title":"J Neuroinflammation"},{"key":"pone.0248309.ref097","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1002\/ana.410420618","article-title":"Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center","volume":"42","author":"E Masliah","year":"1997","journal-title":"Ann Neurol"},{"key":"pone.0248309.ref098","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.3233\/JAD-140393","article-title":"Cofilin rods and aggregates concur with tau pathology and the development of Alzheimer\u2019s disease","volume":"42","author":"T Rahman","year":"2014","journal-title":"J Alzheimers Dis JAD"},{"key":"pone.0248309.ref099","doi-asserted-by":"crossref","first-page":"6367","DOI":"10.1523\/JNEUROSCI.0395-10.2010","article-title":"Memory impairment in transgenic Alzheimer mice requires cellular prion protein","volume":"30","author":"DA Gimbel","year":"2010","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"pone.0248309.ref100","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/acn3.730","article-title":"Anti-PrPC antibody rescues cognition and synapses in transgenic alzheimer mice","volume":"6","author":"TO Cox","year":"2019","journal-title":"Ann Clin Transl Neurol"},{"key":"pone.0248309.ref101","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1038\/cddis.2015.37","article-title":"RanBP9 at the intersection between cofilin and A\u03b2 pathologies: rescue of neurodegenerative changes by RanBP9 reduction","volume":"6","author":"JA Woo","year":"2015","journal-title":"Cell Death Dis"},{"key":"pone.0248309.ref102","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/cdd.2015.5","article-title":"Slingshot-Cofilin activation mediates mitochondrial and synaptic dysfunction via Abeta ligation to beta1-integrin conformers","volume":"22","author":"JA Woo","year":"2015","journal-title":"Cell Death Differ"},{"key":"pone.0248309.ref103","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1007\/s00018-015-1941-z","article-title":"ADF\/cofilin: a crucial regulator of synapse physiology and behavior","volume":"72","author":"MB Rust","year":"2015","journal-title":"Cell Mol Life Sci"},{"key":"pone.0248309.ref104","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1038\/emboj.2010.72","article-title":"Learning, AMPA receptor mobility and synaptic plasticity depend on n-cofilin-mediated actin dynamics","volume":"29","author":"MB Rust","year":"2010","journal-title":"EMBO J"},{"key":"pone.0248309.ref105","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1113\/jphysiol.2011.224873","article-title":"The chemokine CXCL12 and the HIV-1 envelope protein gp120 regulate spontaneous activity of Cajal-Retzius cells in opposite directions","volume":"590","author":"I Marchionni","year":"2012","journal-title":"J Physiol"},{"key":"pone.0248309.ref106","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pharmthera.2017.02.031","article-title":"Peptide regulation of cofilin activity in the CNS: A novel therapeutic approach for treatment of multiple neurological disorders","volume":"175","author":"AE Shaw","year":"2017","journal-title":"Pharmacol Ther"},{"key":"pone.0248309.ref107","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0003-2697(84)90782-6","article-title":"A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids","volume":"138","author":"D Wessel","year":"1984","journal-title":"Anal Biochem"},{"key":"pone.0248309.ref108","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/0003-2697(90)90134-U","article-title":"A filter paper dye-binding assay for quantitative determination of protein without interference from reducing agents or detergents","volume":"190","author":"LS Minamide","year":"1990","journal-title":"Anal Biochem"},{"key":"pone.0248309.ref109","article-title":"Isolation and characterization of a regulated form of actin depolymerizing factor","volume":"122","author":"TE Morgan","year":"1993","journal-title":"Journal of Cell Biology"},{"key":"pone.0248309.ref110","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1093\/oxfordjournals.jbchem.a122919","article-title":"A cofilin-like protein is involved in the regulation of actin assembly in developing skeletal muscle","volume":"106","author":"H Abe","year":"1989","journal-title":"J Biochem (Tokyo)"},{"key":"pone.0248309.ref111","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0006-8993(99)01147-6","article-title":"A quantitative analysis of G-actin binding proteins and the G-actin pool in developing chick brain","volume":"823","author":"N Devineni","year":"1999","journal-title":"Brain Res"}],"container-title":["PLOS 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