{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:51:17Z","timestamp":1791222677111,"version":"4.1.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,2,18]]},"abstract":"<jats:p>\n                    The presence of HIV-1 in latently infected, resting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells has been clearly demonstrated in infected individuals; however, the extent of viral expression and the underlying mechanisms of the persistence of HIV-1 in this viral reservoir have not been fully delineated. Here, we show that resting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from the majority of viremic patients are capable of producing cell-free HIV-1 spontaneously\n                    <jats:italic>ex vivo<\/jats:italic>\n                    . The levels of HIV-1 released by resting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells were not significantly reduced in the presence of inhibitors of cellular proliferation and viral replication. However, resting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from the majority of aviremic patients failed to produce virions, despite levels of HIV-1 proviral DNA and cell-associated HIV-1 RNA comparable to viremic patients. The DNA microarray analysis demonstrated that a number of genes involving transcription regulation, RNA processing and modification, and protein trafficking and vesicle transport were significantly upregulated in resting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells of viremic patients compared to those of aviremic patients. These results suggest that active viral replication has a significant impact on the physiologic state of resting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in infected viremic patients and, in turn, allows release of HIV-1 without exogenous activation stimuli. In addition, given that no quantifiable virions were produced by the latent viral reservoir in the majority of aviremic patients despite the presence of cell-associated HIV-1 RNA, evidence for transcription of HIV-1 RNA in resting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells of aviremic patients should not necessarily be taken as direct evidence for ongoing viral replication during effective therapy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0437640100","type":"journal-article","created":{"date-parts":[[2003,2,18]],"date-time":"2003-02-18T15:04:50Z","timestamp":1045580690000},"page":"1908-1913","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":154,"title":["Gene expression and viral prodution in latently infected, resting CD4\n                    <sup>+<\/sup>\n                    T cells in viremic versus aviremic HIV-infected individuals"],"prefix":"10.1073","volume":"100","author":[{"given":"Tae-Wook","family":"Chun","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Shawn","family":"Justement","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Lempicki","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Glynn","family":"Dennis","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire W.","family":"Hallahan","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Sanford","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punita","family":"Pandya","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda A.","family":"Ehler","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Moir","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony S.","family":"Fauci","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Immunopathogenesis and Bioinformatics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,1,27]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"1","volume":"12","year":"2000","unstructured":"HIV\/AIDS Surv Rep 12, 1\u201344 (2000).","journal-title":"HIV\/AIDS Surv Rep"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13193"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1295"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1291"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5371.1866"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.10958"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295-1284"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/387183a0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)76156-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199905273402101"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199905273402102"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200109070-00005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.2.707-716.2002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8869"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091062498"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.31"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5443.1353"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00217-5"},{"key":"e_1_3_3_19_2","first-page":"165","volume":"73","author":"Ascher M S","year":"1988","unstructured":"M S Ascher, H W Sheppard Clin Exp Immunol 73, 165\u2013167 (1988).","journal-title":"Clin Exp Immunol"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235617"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.9.1277"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.12.1731"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.5.3619"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00102-1"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.131059198"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00238-2"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1201-1313"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(02)02350-8"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0437640100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T14:20:15Z","timestamp":1649773215000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0437640100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1,27]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,2,18]]}},"alternative-id":["10.1073\/pnas.0437640100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0437640100","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1012477.185817","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1,27]]},"assertion":[{"value":"2002-12-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-01-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}