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Here, we investigated the effect of the activation status of CD4<jats:sup>+<\/jats:sup>T cells on the predominance of R5 and X4 HIV-1 variants in different subsets of CD4<jats:sup>+<\/jats:sup>T cells in ex vivo-infected human lymphoid tissues and peripheral blood mononuclear cells (PBMCs). In these cell systems, we examined the sensitivity of HIV replication to reverse transcriptase inhibitors. We demonstrate that R5 HIV-1 variants preferentially produced productive infection in HLA-DR<jats:sup>\u2212<\/jats:sup>CD62L<jats:sup>\u2212<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells. These cells were mostly in the G<jats:sub>1<\/jats:sub>b phase of the cell cycle, divided slowly, and expressed high levels of CCR5. In contrast, X4 HIV-1 variants preferentially produced productive infection in activated HLA-DR<jats:sup>+<\/jats:sup>CD62L<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells, which expressed high levels of CXCR4. The abilities of the nucleoside reverse transcriptase inhibitors (NRTI) zidovudine and lamivudine to stop HIV-1 replication were 20 times greater in activated T cells than in slowly dividing HLA-DR<jats:sup>\u2212<\/jats:sup>CD62L<jats:sup>\u2212<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells. This result, demonstrated both in a highly physiologically relevant ex vivo lymphoid tissue model and in PBMCs, correlated with higher levels of thymidine kinase mRNA in activated than in slowly dividing HLA-DR<jats:sup>\u2212<\/jats:sup>CD62L<jats:sup>\u2212<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells. The non-NRTI nevirapine was equally efficient in both cell subsets. The lymphoid tissue and PBMC-derived cell systems represent well-defined models which could be used as new tools for the study of the mechanism of resistance to HIV-1 inhibitors in HLA-DR<jats:sup>\u2212<\/jats:sup>CD62L<jats:sup>\u2212<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells.<\/jats:p>","DOI":"10.1128\/jvi.80.2.854-865.2006","type":"journal-article","created":{"date-parts":[[2005,12,26]],"date-time":"2005-12-26T15:38:17Z","timestamp":1135611497000},"page":"854-865","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["R5 Variants of Human Immunodeficiency Virus Type 1 Preferentially Infect CD62L<sup>\u2212<\/sup>CD4<sup>+<\/sup>T Cells and Are Potentially Resistant to Nucleoside Reverse Transcriptase Inhibitors"],"prefix":"10.1128","volume":"80","author":[{"given":"Franc\u0327oise","family":"Gondois-Rey","sequence":"first","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U372"},{"name":"IFR 137"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelique","family":"Biancotto","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U372"},{"name":"Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo Antonio","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U372"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lise","family":"Bettendroffer","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U372"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Blazkova","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U372"},{"name":"UMR 599, 27, boulevard Lei Roure, 13009 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina","family":"Trejbalova","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U372"},{"name":"UMR 599, 27, boulevard Lei Roure, 13009 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjorie","family":"Pion","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U372"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U372"},{"name":"UMR 599, 27, boulevard Lei Roure, 13009 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.59.2.284-291.1986"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.4049\/jimmunol.140.7.2171","volume":"140","year":"1988","unstructured":"Akbar, A. 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