{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:45:40Z","timestamp":1792183540460,"version":"4.4.0"},"reference-count":23,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["AIDS Research and Human Retroviruses"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>\n                    Human immunodeficiency virus type 1 (HIV) infection of the central nervous system frequently causes HIV-associated neurocognitive disorders (HAND). The role of HIV Nef and other accessory proteins in HAND pathogenesis is unclear. To determine whether HIV\n                    <jats:italic toggle=\"yes\">nef<\/jats:italic>\n                    undergoes adaptive selection in brain, we cloned 100\n                    <jats:italic toggle=\"yes\">nef<\/jats:italic>\n                    sequences (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200930 brain and\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200970 lymphoid) from four patients with AIDS and HIV-associated dementia (HAD). Normalized nonsynonymous substitutions were more frequent at the divergence of lymphoid and brain sequences, indicating stronger adaptive selection in brain compared to lymphoid tissue. Brain-specific nonsynonymous substitutions were found within an NH\n                    <jats:sub>3<\/jats:sub>\n                    -terminal CTL epitope, the PACS1 binding motif, or positions predicted to be important for activation of the myeloid-restricted Src family tyrosine kinase Hck. These results suggest that adaptive selection of HIV\n                    <jats:italic toggle=\"yes\">nef<\/jats:italic>\n                    in brain may reflect altered requirements for efficient replication in macrophages and brain-specific immune selection pressures.\n                  <\/jats:p>","DOI":"10.1089\/aid.2009.0257","type":"journal-article","created":{"date-parts":[[2010,4,8]],"date-time":"2010-04-08T20:01:35Z","timestamp":1270756895000},"page":"495-500","source":"Crossref","is-referenced-by-count":21,"title":["Evidence for Adaptive Evolution at the Divergence Between Lymphoid and Brain HIV-1\n                    <i>nef<\/i>\n                    Genes"],"prefix":"10.1177","volume":"26","author":[{"given":"Kevin C.","family":"Olivieri","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin A.","family":"Agopian","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joya","family":"Mukerji","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Gabuzda","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute"},{"name":"Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2010,4,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1527"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.2.897-906.1999"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.08.024"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.22.12336-12345.2003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.07.053"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl136"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3192"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.12.6277-6292.2002"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6437"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2308com"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.6.3050-3061.2006"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msm092"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/123.3.603"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msi105"},{"key":"e_1_3_3_16_2","unstructured":"HIV Molecular Immunology 2006\/2007. Los Alamos New Mexico: Los Alamos National Laboratory Theoretical Biology and Biophysics 2007."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi980989q"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.09.009"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2008.0240"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01190-08"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.1106"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.1.62-72.2006"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.5.2712"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020873"}],"container-title":["AIDS Research and Human Retroviruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/aid.2009.0257","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/aid.2009.0257","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/aid.2009.0257","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:12:14Z","timestamp":1777367534000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/aid.2009.0257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,4]]}},"alternative-id":["10.1089\/aid.2009.0257"],"URL":"https:\/\/doi.org\/10.1089\/aid.2009.0257","relation":{},"ISSN":["0889-2229","1931-8405"],"issn-type":[{"value":"0889-2229","type":"print"},{"value":"1931-8405","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4]]}}}