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CD8<jats:sup>+<\/jats:sup>T cells can control infection by producing antiviral cytokines (e.g., gamma interferon or tumor necrosis factor alpha) or by triggering death of infected cells through perforin- or Fas ligand-dependent pathways. Here, we directly evaluated the role of perforin in controlling infection of a lineage I New York isolate of WNV in mice. A genetic deficiency of perforin molecules resulted in higher viral burden in the CNS and increased mortality after WNV infection. In the few perforin-deficient mice that survived initial challenge, viral persistence was observed in the CNS for several weeks. CD8<jats:sup>+<\/jats:sup>T cells required perforin to control WNV infection as adoptive transfer of WNV-primed wild-type but not perforin-deficient CD8<jats:sup>+<\/jats:sup>T cells greatly reduced infection in the brain and spinal cord and enhanced survival of CD8-deficient mice. Analogous results were obtained when wild-type or perforin-deficient CD8<jats:sup>+<\/jats:sup>T cells were added to congenic primary cortical neuron cultures. Taken together, our data suggest that despite the risk of immunopathogenesis, CD8<jats:sup>+<\/jats:sup>T cells use a perforin-dependent mechanism to clear WNV from infected neurons.<\/jats:p>","DOI":"10.1128\/jvi.80.1.119-129.2006","type":"journal-article","created":{"date-parts":[[2005,12,13]],"date-time":"2005-12-13T02:52:45Z","timestamp":1134442365000},"page":"119-129","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":188,"title":["CD8<sup>+<\/sup>T Cells Require Perforin To Clear West Nile Virus from Infected Neurons"],"prefix":"10.1128","volume":"80","author":[{"given":"Bimmi","family":"Shrestha","sequence":"first","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie A.","family":"Samuel","sequence":"additional","affiliation":[{"name":"Molecular Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Molecular Microbiology"},{"name":"Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/313737"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01718310"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(03)00047-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059742"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.9.5374-5385.2005"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01454.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2003.01157.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.4.2578-2586.2003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/088282403322396082"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030732"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a120786"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a120785"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.24.12941-12949.2003"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01309481"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(02)00333-3"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.275"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-73-5-1115"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1499"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0505.990505"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00904.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.7.4761-4766.1996"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/369031a0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7518614"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-68-7-2001"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050588297"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.13.6117-6125.2000"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2003.01167.x"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-69-10-2535"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.3.911"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.17.11457-11466.2005"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"4054","DOI":"10.4049\/jimmunol.136.11.4054","volume":"136","year":"1986","unstructured":"Lampson, L. 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