{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:43:01Z","timestamp":1789645381586,"version":"4.0.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,7,29]],"date-time":"2009-07-29T00:00:00Z","timestamp":1248825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Indiana Genomics Initiative of Indiana University School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>HIV-1 Nef inhibited transwell and transendothelial migration of T cells toward SDF-1\u03b1.<\/jats:p>\n               <jats:p>Lymphocyte trafficking is a multistep, intricate process and involves a number of host factors such as integrins and chemokine receptors on lymphocytes, adhesion molecules on endothelial cells, and chemokines present in the local microenvironment. Previous studies have shown that HIV-1 Nef inhibits T cell chemotaxis in response to the physiological ligand SDF-1\u03b1 [1]. In this study, we aimed to gain a better understanding of the inhibitory mechanisms and to define the molecular determinants of HIV-1 Nef for this phenotype. We showed that HIV-1 Nef inhibited transwell and transendothelial migration of T cells. Specifically, HIV-1 Nef protein impaired T cell chemotaxis toward SDF-1\u03b1 without altering CXCR4 expression. Moreover, we showed that HIV-1 Nef protein down-modulated LFA-1 expression on T lymphocytes and diminished adhesion and polarization of T lymphocytes and as a result, led to decreased migration across the endothelium. Furthermore, we showed that the myristoylation site and \u0394SD domain played important roles in Nef-mediated inhibition of transwell and transendothelial migration and polarization of T lymphocytes; however, different sites or domains were needed for Nef-mediated LFA-1 down-modulation and impaired adhesion of T lymphocyte. Taken together, these results demonstrated that HIV-1 Nef inhibited T lymphocyte migration at multiple steps and suggest that membrane localization and intracellular signaling events likely contribute to the inhibitory effects of Nef on T cell migration and subsequently, the pathobiology of the HIV-1 Nef protein.<\/jats:p>","DOI":"10.1189\/jlb.0409261","type":"journal-article","created":{"date-parts":[[2009,7,30]],"date-time":"2009-07-30T01:06:37Z","timestamp":1248915997000},"page":"1171-1178","source":"Crossref","is-referenced-by-count":31,"title":["HIV-1 Nef-mediated inhibition of T cell migration and its molecular determinants"],"prefix":"10.1093","volume":"86","author":[{"given":"In-Woo","family":"Park","sequence":"first","affiliation":[{"name":"Center for AIDS Research and Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny J","family":"He","sequence":"additional","affiliation":[{"name":"Center for AIDS Research and Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,7,29]]},"reference":[{"key":"2023032912533257800_jlb1171-cit-b1","doi-asserted-by":"crossref","first-page":"46079","DOI":"10.1074\/jbc.M204698200","article-title":"HIV Nef inhibits T cell migration. J","volume":"277","author":"Choe","year":"2002","journal-title":"Biol. Chem."},{"key":"2023032912533257800_jlb1171-cit-b2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S1074-7613(02)00260-1","article-title":"HIV-1 Nef-induced upregulation of DC-SIGN in dendritic cells promotes lymphocyte clustering and viral spread","volume":"16","author":"Sol-Foulon","year":"2002","journal-title":"Immunity"},{"key":"2023032912533257800_jlb1171-cit-b3","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":"Swingler","year":"1999","journal-title":"Nat. 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