{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:07:39Z","timestamp":1790899659643,"version":"4.1.0"},"reference-count":88,"publisher":"American Society for Microbiology","issue":"7","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.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Human immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding of gp120 to receptors on the target cell alters the gp120-gp41 relationship and activates the membrane-fusing capacity of gp41. Interaction of gp120 with the primary receptor, CD4, results in the exposure of the gp120 third variable (V3) loop, which contributes to binding the CCR5 or CXCR4 chemokine receptors. We show here that insertions in the V3 stem or polar substitutions in a conserved hydrophobic patch near the V3 tip result in decreased gp120-gp41 association (in the unliganded state) and decreased chemokine receptor binding (in the CD4-bound state). Subunit association and syncytium-forming ability of the envelope glycoproteins from primary HIV-1 isolates were disrupted more by V3 changes than those of laboratory-adapted HIV-1 envelope glycoproteins. Changes in the gp120 \u03b22, \u03b219, \u03b220, and \u03b221 strands, which evidence suggests are proximal to the V3 loop in unliganded gp120, also resulted in decreased gp120-gp41 association. Thus, a gp120 element composed of the V3 loop and adjacent beta strands contributes to quaternary interactions that stabilize the unliganded trimer. CD4 binding dismantles this element, altering the gp120-gp41 relationship and rendering the hydrophobic patch in the V3 tip available for chemokine receptor binding.<\/jats:p>","DOI":"10.1128\/jvi.02587-09","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T21:09:21Z","timestamp":1264021761000},"page":"3147-3161","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["A V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes the Human Immunodeficiency Virus Envelope Glycoprotein Trimer"],"prefix":"10.1128","volume":"84","author":[{"given":"Shi-Hua","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre\u0301s","family":"Finzi","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Rizzuto","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chin","family":"Huang","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Kwong","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Sodroski","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115"},{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5270.1955"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106229200"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9779"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.9.6006-6013.1994"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03327"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175868"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.7.5294-5300.1999"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81313-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1998.0127"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1196-1244"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.12.7517-7521.1992"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.17.8953-8957.2002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.11.5762"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.12.5541-5549.2001"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/381661a0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.1.129-136.1989"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.6.2452-2456.1989"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81314-8"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090576697"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199305000-00005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.8873-8879.1999"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.2.1160-1164.1998"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80577-2"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007228200"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5263.872"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/316262a0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.4.1428"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1993.9.1007"},{"key":"e_1_3_2_30_2","first-page":"e10000360","volume":"5","year":"2009","unstructured":"Haim, H., Z. Si, N. Madani, L. Wang, J. R. Courter, A. Princiotto, A. Kassa, M. DeGrace, K. McGee-Estrada, M. Mefford, D. Gabuzda, A. B. Smith III, and J. Sodroski. 2009. Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activation state. PLoS Pathog.5:e10000360.","journal-title":"PLoS Pathog."},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2005.21.171"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.5.2416-2420.1990"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.4.2119-2123.1991"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.19.12296-12303.2005"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/096876899294760"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.11.012"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.4049\/jimmunol.160.1.180","volume":"160","year":"1998","unstructured":"Hori, T., H. Sakaida, A. Sato, T. Nakajima, H. Shida, O. Yoshie, and T. Uchiyama. 1998. Detection and delineation of CXCR-4 (fusin) as an entry and fusion cofactor for T-tropic [correction of T cell-tropic] HIV-1 by three different monoclonal antibodies. J. Immunol.160:180-188.","journal-title":"J. Immunol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1145373"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1118398"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00594-09"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.042101"},{"key":"e_1_3_2_42_2","first-page":"102","year":"1998","unstructured":"Korber, B., B. T. Foley, C. Kuiken, S. K. Pillai, and J. G. Sodroski. 1998. Numbering positions in HIV relative to HXB2CG, p. 102-111. In B. Korber, C. L. Kuiken, B. Foley, B. Hahn, F. McCutchan, J. W. Mellors, and J. Sodroski (ed.). Human retroviruses and AIDS 1998. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM.","journal-title":"Human retroviruses and AIDS 1998"},{"key":"e_1_3_2_43_2","unstructured":"HIV sequence compendium 2008 2008"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/31405"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.4.1961-1972.2000"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01188"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030117"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.8.3973-3985.1991"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07159"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.11.6957-6968.2005"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2008.09.005"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.8.4785-4796.1993"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.3.1863-1872.1996"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1357"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.11.4708-4715.2005"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911004107"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.09.021"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(81)90642-5"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5371.1949"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.2.407"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.1.185"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.3.1342-1349.1994"},{"key":"e_1_3_2_63_2","first-page":"41","volume":"348","year":"2006","unstructured":"Seibert, C., W. Ying, S. Gavrilov, F. Tsamis, S. E. Kuhmann, A. Palani, J. R. Tagat, J. W. Clader, S. W. McCombie, B. M. Baroudy, S. O. Smith, T. Dragic, J. P. Moore, and T. P. Sakmar. 2006. Interaction of small molecule inhibitors of HIV-1 entry with CCR5. Virology348:41-54.","journal-title":"Virology"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi800227z"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6095449"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.10.6191-6198.1995"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)39849-7"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.8.6332-6338.1998"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.7.4413-4422.1995"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.6.4694-4703.1998"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.9.3579-3585.1989"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.9.5516-5524.1992"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.7.3978-3988.1993"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/384184a0"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1178746"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.5.2566-2574.1993"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.24.9580"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.1.39-48.1995"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/384179a0"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5371.1884"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.12.6997-7004.1992"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.8.4557-4565.1993"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.10.6068-6077.2005"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.19.9888-9899.2002"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00273-3"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00118-06"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.2.644-655.2002"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05580"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000203"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02587-09","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02587-09","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T14:01:44Z","timestamp":1685368904000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02587-09"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4]]},"references-count":88,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2010,4]]}},"alternative-id":["10.1128\/JVI.02587-09"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02587-09","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4]]},"assertion":[{"value":"2009-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-01-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}