{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:32:11Z","timestamp":1758709931040},"reference-count":39,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2002,1,15]],"date-time":"2002-01-15T00:00:00Z","timestamp":1011052800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2002,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Deletion of the<jats:italic>nef<\/jats:italic>gene from simian immunodeficiency virus (SIV) strain SIVmac239 yields a virus that undergoes attenuated growth in rhesus macaques and offers substantial protection against a subsequent challenge with some SIV wild-type viruses. We used a recently described model to identify sites in which the SIV\u0394<jats:italic>nef<\/jats:italic>vaccine strain replicates and elicits immunity in vivo. A high dose of SIV\u0394<jats:italic>nef<\/jats:italic>was applied to the palatine and lingual tonsils, where it replicated vigorously in this portal of entry at 7 days. Within 2 weeks, the virus had spread and was replicating actively in axillary lymph nodes, primarily in extrafollicular T-cell-rich regions but also in germinal centers. At this time, large numbers of perforin-positive cells, both CD8<jats:sup>+<\/jats:sup>T cells and CD3-negative presumptive natural killer cells, were found in the tonsil and axillary lymph nodes. The number of infected cells and perforin-positive cells then fell. When autopsy studies were carried out at 26 weeks, only 1 to 3 cells hybridized for viral RNA per section of lymphoid tissue. Nevertheless, infected cells were detected chronically in most lymphoid organs, where the titers of infectious virus could exceed by a log or more the titers in blood. Immunocytochemical labeling at the early active stages of infection showed that cells expressing SIV\u0394<jats:italic>nef<\/jats:italic>RNA were CD4<jats:sup>+<\/jats:sup>T lymphocytes. A majority of infected cells were not in the active cell cycle, since 60 to 70% of the RNA-positive cells in tissue sections lacked the Ki-67 cell cycle antigen, and both Ki-67-positive and -negative cells had similar grain counts for viral RNA. Macrophages and dendritic cells, identified with a panel of monoclonal antibodies to these cells, were rarely infected. We conclude that the attenuated growth and protection observed with the SIV\u0394<jats:italic>nef<\/jats:italic>vaccine strain does not require that the virus shift its characteristic site of replication, the CD4<jats:sup>+<\/jats:sup>T lymphocyte. In fact, this immunodeficiency virus can replicate actively in CD4<jats:sup>+<\/jats:sup>T cells prior to being contained by the host, at least in part by a strong killer cell response that is generated acutely in the infected lymph nodes.<\/jats:p>","DOI":"10.1128\/jvi.76.2.688-696.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:55:53Z","timestamp":1027763753000},"page":"688-696","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["The Simian Immunodeficiency Virus \u0394<i>nef<\/i>Vaccine, after Application to the Tonsils of Rhesus Macaques, Replicates Primarily within CD4<sup>+<\/sup>T Cells and Elicits a Local Perforin-Positive CD8<sup>+<\/sup>T-Cell Response"],"prefix":"10.1128","volume":"76","author":[{"given":"Christiane","family":"Stahl-Hennig","sequence":"first","affiliation":[{"name":"German Primate Center, 37077 Go\u0308ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph M.","family":"Steinman","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Ten Haaft","sequence":"additional","affiliation":[{"name":"Department of Virology, Biomedical Primate Research Centre, 2288 GJ Rijswijk, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"U\u0308berla","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology, Ruhr University, Bochum 44780, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Stolte","sequence":"additional","affiliation":[{"name":"German Primate Center, 37077 Go\u0308ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sem","family":"Saeland","sequence":"additional","affiliation":[{"name":"Laboratory for Immunological Research, Schering-Plough, 69571 Dardilly, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klara","family":"Tenner-Racz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Ko\u0308rber Laboratory for AIDS Research, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Racz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Ko\u0308rber Laboratory for AIDS Research, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.8.6094-6099.1997"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058915"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5267.1486"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5491.486"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.0026"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90417-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.8419"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1470917"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80615-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.16.7538-7547.2000"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.14031"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80694-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.4049\/jimmunol.133.4.1710","volume":"133","year":"1984","unstructured":"Gerdes, J., H. 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