{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:43:18Z","timestamp":1790800998753,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01 MH107333"],"award-info":[{"award-number":["R01 MH107333"]}],"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 MH118139"],"award-info":[{"award-number":["R01 MH118139"]}],"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":["R21 MH108458"],"award-info":[{"award-number":["R21 MH108458"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>C\u2010C chemokine receptor 5 (CCR5) is a major coreceptor for Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) cell entry; however, its role in brain pathogenesis is largely understudied. Thus, we sought to examine cell type\u2010specific protein expression of CCR5 during SIV infection of the brain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined occipital cortical tissue from uninfected rhesus macaques and SIV\u2010infected animals with or without encephalitis using immunohistochemistry and immunofluorescence microscopy to determine the number and distribution of CCR5\u2010positive cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>An increase in the number of CCR5+ cells in the brain of SIV\u2010infected animals with encephalitis was accounted for by increased CD3+CD8+ cells expressing CCR5, but not by increased CCR5+ microglia or perivascular macrophages (PVMs), and a concurrent decrease in the percentage of CCR5+ PVMs was observed. Levels of CCR5 and SIV Gag p28 protein expression were examined on a per\u2010cell basis, and a significant, negative relationship was established indicating decreased CCR5 expression in productively infected cells. While investigating the endocytosis\u2010mediated CCR5 internalization as a mechanism for CCR5 downregulation, we found that phospho\u2010ERK1\/2, an indicator of clathrin\u2010mediated endocytosis, was colocalized with infected PVMs and that macrophages from infected animals showed significantly increased expression of clathrin heavy chain 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings show a shift in CCR5\u2010positive cell types in the brain during SIV pathogenesis with an increase in the number of CCR5+ CD8 T cells, and downregulated CCR5 expression on infected PVMs, likely through ERK1\/2\u2010driven, clathrin\u2010mediated endocytosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.3126","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T04:45:23Z","timestamp":1687841123000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Downregulation of CCR5 on brain perivascular macrophages in simian immunodeficiency virus\u2010infected rhesus macaques"],"prefix":"10.1002","volume":"13","author":[{"given":"Julian B.","family":"Hattler","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Cell Biology Eastern Virginia Medical School Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek L.","family":"Irons","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Cell Biology Eastern Virginia Medical School Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Health Systems and Population Health Sciences Tilman J. Fertitta Family College of Medicine, University of Houston Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9964-185X","authenticated-orcid":false,"given":"Woong\u2010Ki","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Cell Biology Eastern Virginia Medical School Norfolk Virginia USA"},{"name":"Division of Microbiology Tulane National Primate Research Center Covington Louisiana USA"},{"name":"Department of Microbiology and Immunology Tulane University School of Medicine New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12808"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0409\u2010371"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.11.5762"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365\u2010019\u201000755\u2010w"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.1993.tb26259.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2008.03.026"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.4005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32900"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2225"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101027\u20104"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02333\u201014"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00222\u201018"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802905"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000074"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/13550280490505382"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481\u2010018\u20109809\u20102"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0046\u20108177(91)90293\u2010X"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.687296"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.9.5429"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030\u2010200307250\u201000004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.02.058"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.22.12346\u201012351.2003"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.3.785"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432\u20101033.2003.03918.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1515\/med\u20102018\u20100062"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12977\u2010018\u20100388\u20103"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04\u201008\u20100687"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.6.1281"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11904\u2010019\u201000445\u20106"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095767"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01109\u201010"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2016.0198"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1482"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01358"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500708"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.10.5582"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802703R"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13594"},{"key":"e_1_2_8_40_1","first-page":"5447","article-title":"Maraviroc: A review of its use in HIV infection and beyond","volume":"9","author":"Woollard S. 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