{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:04:58Z","timestamp":1791119098891,"version":"4.1.0"},"reference-count":26,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5314","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1997,5,9]]},"abstract":"<jats:p>In lymphoid tissue, where human immunodeficiency virus\u2013type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by \u22653.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared &gt;99.9 percent of virus from the secondary lymphoid tissue reservoir.<\/jats:p>","DOI":"10.1126\/science.276.5314.960","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:45:15Z","timestamp":1027763115000},"page":"960-964","source":"Crossref","is-referenced-by-count":444,"title":["Kinetics of Response in Lymphoid Tissues to Antiretroviral Therapy of HIV-1 Infection"],"prefix":"10.1126","volume":"276","author":[{"given":"Winston","family":"Cavert","sequence":"first","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan W.","family":"Notermans","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Staskus","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Wietgrefe","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Zupancic","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Gebhard","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Henry","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. 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Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap","family":"Goudsmit","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven A.","family":"Danner","sequence":"additional","affiliation":[{"name":"W. Cavert, K. Staskus, S. W. Wietgrefe, M. Zupancic, K. Gebhard, Z.-Q. Zhang, A. T. 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Haase, Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"D. W. Notermans, J. Goudsmit, S. A. Danner, Division of Infectious Diseases, Tropical Medicine, and AIDS and National AIDS Therapy Center, Academic Medical Center, University of Amsterdam, Post Office Box 22700, 1100 DE Amsterdam, Netherlands."},{"name":"K. Henry, HIV Program, St. Paul\u2013Ramsey Medical Center, St. Paul, MN 55101, USA, and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"R. Mills, Abbott Laboratories, Abbott Park, IL 60064, USA."},{"name":"H. McDade, Glaxo Wellcome Research and Development, Greenford-Middlesex UB6 0HE, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5265.1167"},{"key":"e_1_3_1_2_3","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJM199610103351502","volume":"335","author":"Katzenstein D. A.","year":"1996","unstructured":"Katzenstein D. A., et al., N. Engl. J. Med. 335, 1091 (1996);","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_1_2_4","first-page":"426","volume":"334","author":"O\u2019Brien W. A.","year":"1996","unstructured":"O\u2019Brien W. A., et al., ibid. 334, 426 (1996).","journal-title":"ibid."},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1126\/science.274.5289.985","volume":"274","author":"Haase A. T.","year":"1996","unstructured":"Haase A. T., et al., Science 274, 985 (1996).","journal-title":"Science"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/infdis\/173.4.849","volume":"173","author":"Cohen O. J.","year":"1996","unstructured":"Cohen O. J., et al., J. Infect. Dis. 173, 849 (1996).","journal-title":"J. Infect. Dis."},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"6017","DOI":"10.1073\/pnas.92.13.6017","volume":"92","author":"Cohen O. J.","year":"1995","unstructured":"Cohen O. J., et al., Proc. Natl. Acad. Sci. U.S.A. 92, 6017 (1995).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/infdis\/174.2.404","volume":"174","author":"Lafeuillade A.","year":"1996","unstructured":"Lafeuillade A., et al., J. Infect. Dis. 174, 404 (1996).","journal-title":"J. Infect. Dis."},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0194-59989670252-8","volume":"114","author":"Faust R. A.","year":"1996","unstructured":"Faust R. A., et al., Otolaryngol. Head Neck Surg. 114, 593 (1996).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"e_1_3_1_8_2","unstructured":"Protocol NUCB 2019. Participants underwent serial venipuncture for T cell subsets plasma HIV RNA and genotypic virology."},{"key":"e_1_3_1_9_2","unstructured":"D. W. Notermans et al. in preparation."},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/373117a0","volume":"373","author":"Wei X.","year":"1995","unstructured":"Wei X., et al., Nature 373, 117 (1995);","journal-title":"Nature"},{"key":"e_1_3_1_10_3","unstructured":"; D. D. Ho et al. ibid. p. 123."},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5255.1582"},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1600-065X.1980.tb01039.x","volume":"53","author":"Mandel T. E.","year":"1980","unstructured":"Mandel T. E., et al., Immunol. Rev. 53, 29 (1980).","journal-title":"Immunol. Rev."},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/377740a0","volume":"377","author":"Heath S. L.","year":"1995","unstructured":"Heath S. L., et al., Nature 377, 740 (1995).","journal-title":"Nature"},{"key":"e_1_3_1_14_2","unstructured":"Seventeen individuals underwent at least one tonsil biopsy. Four subjects withdrew from the LT substudy because early biopsies provided insufficient LT for analysis and three withdrew for clinical reasons. Of the 10 remaining all had evaluable tissue at three or all four of the time points and all had final biopsies at 6 months. Their median baseline peripheral absolute CD4 + cell count was 194 cells per cubic millimeter."},{"key":"e_1_3_1_15_2","unstructured":"Viral load in FDC and MNC pools and frequency of infected cells per gram of LT were determined at baseline (2) and at 24 weeks (18) as described. Half-lives for the FDC-associated viral load and the frequency of MNCs with >20 copies of viral RNA per cell were estimated by solving the equation t 1\/2 = n \/[log(mean v 0 \/mean v n )\/log 2] where n = number of days and v = viral load at each time point. The initial turnover rates were calculated from the t 1\/2 values the mean pool sizes shown in Table 1 and the number of days of treatment. Because the FDC pool stores most virus produced the simplest explanation for the early rapid elimination of FDC-associated virus is that it is a result of treatment-induced reductions in MNC virus manufacture. Dividing the initial turnover per day in the FDC pool by the initial turnover per day of MNC thus gives an estimate of the number of copies of viral RNA per productively infected MNC."},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7824947"},{"key":"e_1_3_1_17_2","first-page":"9","volume":"143","author":"Brahic M.","year":"1989","unstructured":"Brahic M., Haase A. T., Curr. Top. Microbiol. Immunol. 143, 9 (1989).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_1_18_2","unstructured":"To unambiguously identify the cell type in which HIV RNA is detectable we combined in situ hybridization and immunohistochemical staining with mAb to CD68 a macrophage-specific marker. Tissue sections were deparaffinized with xylene cleared with ethanol and hydrated in diethyl pyrocarbonate (DEPC) water. CD68 antigen reactivity with the mAb was enhanced by heating the slides for 10 min at 80% power of a 1000-W microwave oven in 10 mM citrate buffer (pH 6.0). After cooling for 30 min the sections were acetylated prehybridized and then hybridized with antisense 35 S-labeled HIV RNA probe. After post-hybridization washes nonspecific binding of antibodies was blocked by immersing the sections in 5% nonfat milk in phosphate-buffered saline (PBS) for 30 min. Sections were then treated with a 1:300 dilution of CD68 mAb (Dako Carpinteria CA) at 4\u00b0C overnight. After washing slides were developed with a peroxidase-conjugated secondary antibody and diaminobenzidene substrate according the manufacturer\u2019s protocol (ABC Elite kit; Vector Labs Burlingame CA). The sections were then washed in PBS and 0.1\u00d7 PBS dehydrated in ethanol containing 0.3 M ammonium acetate and coated with nuclear track emulsion. After development the slides were briefly counterstained in hematoxylin."},{"key":"e_1_3_1_19_2","unstructured":"Longer autoradiographic exposures of 7 to 10 days increase the sensitivity of in situ hybridization. To determine the limits of detection of HIV RNA we first measured the background signal over MNCs and FDCs from the binding of antisense HIV RNA probe to LT sections of HIV-seronegative individuals and from the nonspecific binding of the sense HIV RNA probe to LT sections of HIV-seropositive individuals. Dividing the number of silver grains determined by quantitative image analysis in randomly selected areas by the number of cells in those areas provided a maximum estimate of background. Backgrounds by both approaches were one or two silver grains per MNC for 10-day exposures. An MNC with one HIV RNA copy will show 24 grains over background with such long exposures and will be easily identified. The lower limit of detection for MNCs is therefore about one copy of HIV RNA per cell. For the FDCs we measured the area of germinal centers (GCs) and determined their average backgrounds to be 2.3 grains per 10 \u20133 mm 2 . The Poisson probability that x number of grains differs from a background average of m grains is 1 \u2013 m x exp( \u2013m ) m ( x !) \u20131 (22). For a probability P > 0.99 that there is a significant increase over background in a GC the signal over FDCs would have to be more than seven grains per 10 \u20133 mm 2 . For example the GC shown in Fig. 4B had 450 grains in an area of 0.05 mm 2 or 9 grains per 10 \u20133 mm 2 and thus fulfills this condition; from the number of silver grains over background we calculate that there are 146 copies of HIV-1 RNA in this GC. The limits of detection of viral RNA for infected cells expressed per gram of tissue depends on the number and area of the sections examined. For example we usually randomly sampled and exhaustively screened 40 8-\u03bcm sections averaging \u223c5 mm 2 each cumulatively equivalent to \u223c1.2 mg of tissue. If these sections contained no MNCs with HIV-1 RNA this frequency would be <\u223c625 cells per gram. For the FDCs we determined with the long exposure an average detectable copy number of \u223c20 copies per GC and thus a lower detection threshold of \u223c10 4 copies per gram of LT."},{"key":"e_1_3_1_20_2","unstructured":"For DNA PCR analysis nucleic acids from guanidine-HCl extracts of flash-frozen tonsil biopsies were precipitated out of 70% ethanol pelleted ethanol-washed and resuspended in 10 mM tris-HCl (pH 8.0) containing 1 mM EDTA and 0.5% SDS. The suspensions were then treated with ribonuclease A (RNase A 20 \u03bcg\/ml) for 1 hour at 37\u00b0C incubated with proteinase K (100 \u03bcg\/ml) at 50\u00b0C for 3 hours and finally extracted with phenol phenol\/chloroform and chloroform before ethanol precipitation and wash. Control DNA with and without HIV-1 proviral DNA was similarly extracted from ACH-2 cells and H-9 cells respectively. Nested PCR was performed with the use of two sets of primers designed to amplify a conserved region of HIV-1 gag. The primary amplification reactions contained 1 \u03bcg of each DNA specimen 1\u00d7 PCRII reaction buffer (Perkin-Elmer) 2.5 mM MgCl 2 200 mM deoxynucleotide triphosphates 1 \u03bcM primers (30-nucleotide oligomers: 5\u2032-GTCAGCCAAAATTACCCTATAGTGCAGAAC-3\u2032 5\u2032-ACATAGTCTCTAAAGGGTTCCTTTGGTCCT-3\u2032) and Amplitaq polymerase (0.08 U\/ml Perkin-Elmer) in a 100-ml volume. DNA was amplified 25 cycles at 94\u00b0C for 45 s 60\u00b0C for 45 s and 72\u00b0C for 3 min. The secondary (nested) reactions contained 2 \u03bcl of the primary amplified reaction mixture with otherwise the same constituents except for primers (20-nucleotide oligomers: 5\u2032-TCACCTAGAACTTTAAATGC-3\u2032 5\u2032-ATTTAATCCCAGGATTATCC-3\u2032). This second amplification was 30 cycles with the same cycling parameters. RT-PCR reactions were performed on RNA containing fractions of the guanidine tissue homogenates and were processed and PCR-amplified in the same manner except that deoxyribonuclease pretreatment was substituted for RNase A pretreatment and reverse transcription using rTth polymerase (Perkin-Elmer) was included before amplification. Southern (DNA) blots were hybridized to a cocktail containing three oligonucleotide probes labeled at the 3\u2032 termini with [ 32 P]deoxyadenosine triphosphate specific for sequences internal to the nesting primers (30-nucleotide oligomers: 5\u2032-CATGGGTAAAAGTAGTAGAAGAGAAGGCTT-3\u2032 5\u2032-GGGACATCAAGCAGCCATGCAAATGTTAAA-3\u2032 5\u2032-CCAAGGGGAAGTGACATAGCAGGAACTACT-3\u2032)."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/362359a0","volume":"362","author":"Embretson J.","year":"1993","unstructured":"Embretson J., et al., Nature 362, 359 (1993).","journal-title":"Nature"},{"key":"e_1_3_1_22_2","unstructured":"This marked reduction in lymphoid viral load translates into a slow but commensurate repopulation of the LT with CD4 + T lymphocytes (Z.-Q. Zhang et al. in preparation)."},{"key":"e_1_3_1_23_2","unstructured":"A. T. Haase in In Situ Hybridization: Applications to Neurobiology K. L. Valentino J. H. Eberwine J. D. Barchas Eds. (Oxford Univ. Press New York 1987) pp. 197\u2013219."},{"key":"e_1_3_1_24_2","unstructured":"We thank P. Dailey for technical assistance; C. O\u2019Neill T. Leonard and G. Sedgewick for assistance with preparation of the manuscript and figures; and J. Leonard and G. Goodwin for clinical support. Supported by NIH grants AI 25017 and AI 28246."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.276.5314.960","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T05:45:47Z","timestamp":1705124747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.276.5314.960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5,9]]},"references-count":26,"journal-issue":{"issue":"5314","published-print":{"date-parts":[[1997,5,9]]}},"alternative-id":["10.1126\/science.276.5314.960"],"URL":"https:\/\/doi.org\/10.1126\/science.276.5314.960","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5,9]]}}}