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Infections of the CNS with highly cytopathic neurotropic viruses, such as West Nile virus (WNV), however, require the parenchymal penetration of T lymphocytes for virus clearance and survival, suggesting that perivascular localization might hinder antiviral immune responses during WNV encephalitis. Using human and murine brain specimens from individuals with WNV encephalitis, we evaluated the expression of CXCL12 and its receptor, CXCR4, at the BBB and tested the hypothesis that inhibition of CXCR4 would promote T lymphocyte entry into the CNS parenchyma and increase viral clearance. Antagonism of CXCR4 significantly improved survival from lethal infection through enhanced intraparenchymal migration of WNV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells within the brain, leading to reduced viral loads and, surprisingly, decreased immunopathology at this site. The benefits of enhanced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration suggest that pharmacologic targeting of CXCR4 may have therapeutic utility for the treatment of acute viral infections of the CNS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0800898105","type":"journal-article","created":{"date-parts":[[2008,8,4]],"date-time":"2008-08-04T21:27:56Z","timestamp":1217885276000},"page":"11270-11275","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":136,"title":["CXCR4 antagonism increases T cell trafficking in the central nervous system and improves survival from West Nile virus encephalitis"],"prefix":"10.1073","volume":"105","author":[{"given":"Erin E.","family":"McCandless","sequence":"first","affiliation":[{"name":"Departments of *Pathology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Departments of *Pathology and Immunology,"},{"name":"Internal Medicine,"},{"name":"Molecular Microbiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn S.","family":"Klein","sequence":"additional","affiliation":[{"name":"Departments of *Pathology and Immunology,"},{"name":"Internal Medicine,"},{"name":"Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,8,12]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1130"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.8.4779"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.21.13509-13518.2005"},{"key":"e_1_3_3_4_2","first-page":"59","article-title":"Neuropathology of the brain and spinal cord in human West Nile virus infection","volume":"23","author":"Bouffard JP","year":"2004","unstructured":"JP Bouffard, MA Riudavets, R Holman, EJ Rushing, Neuropathology of the brain and spinal cord in human West Nile virus infection. 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