{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:27:39Z","timestamp":1790242059246,"version":"4.1.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2014,4,4]],"date-time":"2014-04-04T00:00:00Z","timestamp":1396569600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0093699","type":"journal-article","created":{"date-parts":[[2014,4,4]],"date-time":"2014-04-04T20:32:50Z","timestamp":1396643570000},"page":"e93699","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["HIV-1 Nef Impairs Key Functional Activities in Human Macrophages through CD36 Downregulation"],"prefix":"10.1371","volume":"9","author":[{"given":"Eleonora","family":"Olivetta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Tirelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Chiozzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Scazzocchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio","family":"Romano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Arenaccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,4,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.coi.2005.11.008","article-title":"The mononuclear phagocyte system","volume":"18","author":"DA Hume","year":"2006","journal-title":"Curr Opin Immunol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1046\/j.1365-2567.2002.01404.x","article-title":"Peroxisome-proliferator-activated-receptor gamma (PPAR\u03b3) independent induction of CD36 in THP-1 monocytes by retinoic acid","volume":"106","author":"S Han","year":"2002","journal-title":"Immunology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1172\/JCI14006","article-title":"CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism","volume":"108","author":"M Febbraio","year":"2001","journal-title":"J Clin Invest"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S1050-1738(03)00026-4","article-title":"Pathophysiology of Human Genetic CD36 Deficiency","volume":"13","author":"K Hirano","year":"2003","journal-title":"Trends Cardiovasc Med"},{"key":"ref5","first-page":"re3","article-title":"CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and Behavior","volume":"2(72)","author":"RL Silverstein","year":"2009","journal-title":"Sci Signal"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1111\/j.1462-5822.2009.01326.x","article-title":"Scavenger receptors: role in innate immunity and microbial pathogenesis","volume":"11","author":"T Areschoug","year":"2009","journal-title":"Cell Microbiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1126\/science.1116006","article-title":"Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection","volume":"309","author":"JA Philips","year":"2005","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1083\/jcb.200501113","article-title":"Response to <italic>Staphylococcus aureus<\/italic> requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain","volume":"170","author":"LM Stuart","year":"2005","journal-title":"J Cell Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"7147","DOI":"10.4049\/jimmunol.181.10.7147","article-title":"Role of human CD36 in bacterial recognition, phagocytosis, and pathogen-induced JNK-mediated signaling","volume":"181","author":"IN Baranova","year":"2008","journal-title":"J Immunol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"432","DOI":"10.3109\/08830185.2012.737073","article-title":"HIV-1 Nef in macrophage-mediated disease pathogenesis","volume":"31(6)","author":"SL Lamers","year":"2012","journal-title":"Int Rev Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/0092-8674(91)90097-I","article-title":"Importance of the nef gene for maintenance of high virus loads and for development of AIDS","volume":"65","author":"HW Kestler 3rd","year":"1991","journal-title":"Cell"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.mam.2010.05.003","article-title":"Human immunodeficiency virus (HIV) type-1, HIV-2 and simian immunodeficiency virus Nef proteins","volume":"31","author":"N Laguette","year":"2010","journal-title":"Mol Aspects Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"505","DOI":"10.2174\/157016211798842080","article-title":"Nef performance in macrophages: the master orchestrator of viral persistence and spread","volume":"9","author":"Y Ghiglione","year":"2011","journal-title":"Curr HIV Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0022-2143(98)90041-5","article-title":"Impaired phagocyte oxidative capacity in patients with human immunodeficiency virus infection","volume":"132","author":"DL Pitrak","year":"1998","journal-title":"J Lab Clin Med"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1042\/BJ20042139","article-title":"HIV-1 Nef regulates the release of superoxide anion from human macrophages","volume":"390","author":"E Olivetta","year":"2005","journal-title":"Biochem J"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/jcb.22041","article-title":"HIV-1 Nef induces p47(phox) phosphorylation leading to a rapid superoxide anion release from the U937 human monoblastic cell line","volume":"106","author":"E Olivetta","year":"2009","journal-title":"J Cell Biochem"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/12433","article-title":"HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages","volume":"5","author":"S Swingler","year":"1999","journal-title":"Nat Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"25605","DOI":"10.1074\/jbc.M103244200","article-title":"HIV-1 Nef promotes survival of myeloid cells by a Stat3-dependent pathway","volume":"276","author":"SD Briggs","year":"2001","journal-title":"J Biol Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1006\/jmbi.1999.2849","article-title":"Induction of activator protein 1 (AP-1) in macrophages by human immunodeficiency virus type-1 NEF is a cell-type-specific response that requires both hck and MAPK signalling events","volume":"290","author":"TE Biggs","year":"1999","journal-title":"J Mol Biol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.4049\/jimmunol.170.4.1716","article-title":"HIV-1 Nef induces the release of inflammatory factors from human monocyte\/macrophages: involvement of Nef endocytotic signals and NF-kappa B activation","volume":"170","author":"E Olivetta","year":"2003","journal-title":"J Immunol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1182\/blood.V98.9.2752","article-title":"HIV-1 Nef activates STAT1 in human monocytes\/macrophages through the release of soluble factors","volume":"98","author":"M Federico","year":"2001","journal-title":"Blood"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1189\/jlb.0403161","article-title":"Human immunodeficiency virus type 1 (HIV-1) Nef activates STAT3 in primary human monocyte\/macrophages through the release of soluble factors: involvement of Nef domains interacting with the cell endocytotic machinery","volume":"74","author":"Z Percario","year":"2003","journal-title":"J Leuk Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1006\/bcmd.2002.0502","article-title":"In Vitro mass production of human erythroid cells from the blood of normal donors and of thalassemic patients","volume":"28","author":"G Migliaccio","year":"2002","journal-title":"Blood Cells Mol Dis"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/prot.20544","article-title":"Co-translational myristoylation alters the quaternary structure of HIV-1 Nef in solution","volume":"60","author":"CA Dennis","year":"2005","journal-title":"Proteins"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0022-1759(82)90005-9","article-title":"The inhibitory effect of polymyxin B on endotoxin-induced endogenous pyrogen production","volume":"52","author":"GW Duff","year":"1982","journal-title":"J Immunol Methods"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1182\/blood.V98.9.2752","article-title":"HIV-1 Nef activates STAT1 in human monocytes\/macrophages through the release of soluble factors","volume":"98","author":"M Federico","year":"2001","journal-title":"Blood"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e36632","DOI":"10.1371\/journal.pone.0036632","article-title":"Co-Stimulation of PAFR and CD36 Is Required for oxLDL-Induced Human Macrophages Activation","volume":"7(5)","author":"FJ Rios","year":"2012","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1093\/jn\/134.4.785","article-title":"Extra virgin olive oil biophenols inhibit cell-mediated oxidation of LDL by increasing the mRNA transcription of glutathione-related enzymes","volume":"134","author":"R Masella","year":"2004","journal-title":"J. Nutr"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0022-2275(20)31644-8","article-title":"OxLDL induces macrophage \u03b3-GCS-HS protein expression: a role for oxLDL-associated lipid hydroperoxide in GSH synthesis","volume":"42","author":"L Shen","year":"2001","journal-title":"J. Lipid Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0009-3084(87)90071-5","article-title":"Lipid peroxides and human diseases. Chem. Phys","volume":"45","author":"K Yagi","year":"1987","journal-title":"Lipids"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1086\/648478","article-title":"Bacteriophage therapy of Salmonella enterica: a fresh appraisal of bacteriophage therapy","volume":"201","author":"R Capparelli","year":"2010","journal-title":"J Infect Dis"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0022-1759(86)90322-4","article-title":"A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor\/tumor necrosis factor from human monocytes","volume":"95","author":"T Espevik","year":"1986","journal-title":"J Immunol Methods"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"1\u20132","author":"T Mosmann","year":"1983","journal-title":"J Immunol Methods 65, Issues"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Tirelli V, Ghinassi B, Migliaccio AR, Whitsett C, Masiello F, <etal>et al<\/etal>.. (2011) Phenotypic definition of the progenitor cells with erythroid differentiation potential present in human adult blood. Stem Cells. Int Article ID 602483, doi:10.4061\/2011\/602483.","DOI":"10.4061\/2011\/602483"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"S Akira","year":"2006","journal-title":"Cell"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"6452","DOI":"10.4049\/jimmunol.0901374","article-title":"CD36 and TLR interactions in inflammation and phagocytosis: implications for malaria","volume":"183","author":"LK Erdman","year":"2009","journal-title":"J Immunol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/ni.1836","article-title":"CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer","volume":"11","author":"CR Stewart","year":"2010","journal-title":"Nat Immunol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1006\/bbrc.1999.1193","article-title":"Lipopolysaccharide inhibits the expression of the scavenger receptor Cla-1 in human monocytes and macrophages","volume":"262","author":"C Buechler","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cyto.2012.06.020","article-title":"Functional consequences of CD36 downregulation by TLR signals","volume":"60","author":"C Zamora","year":"2012","journal-title":"Cytokine"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1086\/654817","article-title":"Circulating Nef Induces Dyslipidemia in SIV-Infected Macaques by Suppressing Cholesterol Efflux","volume":"202","author":"BF Asztalos","year":"2010","journal-title":"J Infect Dis"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.4049\/jimmunol.1100350","article-title":"Class B scavenger receptor types I and II and CD36 mediate bacterial recognition and proinflammatory signaling induced by Escherichia coli, lipopolysaccharide, and cytosolic chaperonin 60","volume":"188","author":"IN Baranova","year":"2012","journal-title":"J Immunol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"R22","DOI":"10.1186\/ar2133","article-title":"Tumor necrosis factor alpha and adalimumab differentially regulate CD36 expression in human monocytes","volume":"9","author":"JF Boyer","year":"2007","journal-title":"Arthritis Res Ther"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0014-5793(96)00859-9","article-title":"Soluble Nef antigen of HIV-1 is cytotoxic for human CD4+ T cells","volume":"393","author":"Y Fujii","year":"1996","journal-title":"FEBS Lett"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1165\/ajrcmb.18.6.3059","article-title":"Surfactant protein-A reduces binding and phagocytosis of <italic>pneumocystis carinii<\/italic> by human alveolar macrophages in vitro","volume":"18","author":"H Koziel","year":"1998","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1165\/ajrcmb.23.4.4084","article-title":"Alveolar macrophages from human immunodeficiency virus-infected persons demonstrate impaired oxidative burst response to <italic>Pneumocystis carinii<\/italic> in vitro","volume":"23","author":"H Koziel","year":"2000","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ref46","first-page":"983","article-title":"Impaired macrophage phagocytosis of apoptotic neutrophils in patients with human immunodeficiency virus type 1 infection","volume":"9","author":"D Torre","year":"2002","journal-title":"Clin Diagn Lab Immunol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S1386-6532(02)00123-3","article-title":"Defective phagocytosis by human monocyte\/macrophages following HIV-1 infection: underlying mechanisms and modulation by adjunctive cytokine therapy","volume":"26","author":"K Kedzierska","year":"2003","journal-title":"J Clin Virol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.4049\/jimmunol.168.6.2895","article-title":"HIV-1 down-modulates gamma signaling chain of Fc gamma R in human macrophages: a possible mechanism for inhibition of phagocytosis","volume":"168","author":"K Kedzierska","year":"2002","journal-title":"J Immunol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.1182\/blood-2009-12-259473","article-title":"Inhibition of phagocytosis in HIV-1-infected macrophages relies on Nef-dependent alteration of focal delivery of recycling compartments","volume":"115","author":"J Mazzolini","year":"2010","journal-title":"Blood"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature03253","article-title":"CD36 is a sensor of diacylglycerides","volume":"433","author":"K Hoebe","year":"2005","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0092-8674(89)90406-6","article-title":"CD36 directly mediates cytoadherence of <italic>Plasmodium falciparum<\/italic> parasitized erythrocytes","volume":"58","author":"P Oquendo","year":"1989","journal-title":"Cell"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1128\/IAI.71.1.393-400.2003","article-title":"CD36-mediated nonopsonic phagocytosis of erythrocytes infected with stage I and IIA gametocytes of <italic>Plasmodium falciparum<\/italic>","volume":"71","author":"TG Smith","year":"2003","journal-title":"Infect Immun"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1074\/jbc.275.2.1241","article-title":"Transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-activated receptor-gamma","volume":"275","author":"J Han","year":"2000","journal-title":"J Biol Chem"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.cardiores.2007.03.010","article-title":"CD36 and macrophages in atherosclerosis","volume":"75","author":"S Collot-Teixeira","year":"2007","journal-title":"Cardiovasc Res"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Renga B, Francisci D, D&apos;Amore C, Schiaroli E, Carino A, <etal>et al<\/etal>.. (2012) HIV-1 infection is associated with changes in nuclear receptor transcriptome, pro-inflammatory and lipid profile of monocytes. BMC Infect Dis doi: 10.1186\/1471-2334-12-274.","DOI":"10.1186\/1471-2334-12-274"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"e35924","DOI":"10.1371\/journal.pone.0035924","article-title":"The HIV matrix protein p17 subverts nuclear receptors expression and induces a STAT1-dependent proinflammatory phenotype in monocytes","volume":"7","author":"B Renga","year":"2012","journal-title":"PLoS One"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/00002030-200202150-00006","article-title":"CD36 deficiency induced by antiretroviral therapy","volume":"16","author":"L Serghides","year":"2002","journal-title":"AIDS"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1172\/JCI200316261","article-title":"HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages","volume":"111","author":"J Dressman","year":"2003","journal-title":"J Clin Invest"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.freeradbiomed.2004.12.030","article-title":"CD36 overexpression in ritonavir-treated THP-1 cells is reversed by alpha-tocopherol","volume":"38","author":"A Munteanu","year":"2005","journal-title":"Free Radic Biol Med"},{"key":"ref60","first-page":"628","article-title":"The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation. J Infect Dis","volume":"207","author":"ER Feeney","year":"2013"},{"key":"ref61","first-page":"310","article-title":"Increased CD36 expression on circulating monocytes during HIV infection. J Acquir Immune Defic Syndr","volume":"38","author":"L Meroni","year":"2005"},{"key":"ref62","doi-asserted-by":"crossref","unstructured":"Boccara F (2008) Cardiovascular complications and atherosclerotic manifestations in the HIV-infected population: type, incidence and associated risk factors. AIDS Suppl 3: S19\u201326. doi: 10.1097\/01.","DOI":"10.1097\/01"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1310\/7381-M1YD-RTV5-4RYT","article-title":"Concentration of circulating oxidized LDL in HIV-infected patients treated with antiretroviral agents: relation to HIV-related lipodystrophy","volume":"7","author":"M Duong","year":"2006","journal-title":"HIV Clin Trials"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1046\/j.1365-2362.2002.00989.x","article-title":"LDL-receptors expression in HIV-infected patients: relations to antiretroviral therapy, hormonal status, and presence of lipodystrophy","volume":"32","author":"JM Petit","year":"2002","journal-title":"Eur J Clin Invest"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.3181\/0805-RM-144","article-title":"Ritonavir increases CD36, ABCA1 and CYP27 expression in THP-1 macrophages","volume":"233","author":"J Pou","year":"2008","journal-title":"Exp Biol Med"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0093699","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T20:27:57Z","timestamp":1648758477000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0093699"}},"subtitle":[],"editor":[{"given":"Bruno","family":"Verhasselt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,4,4]]},"references-count":65,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,4,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0093699","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,4]]}}}