Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization
Antibody-mediated neutralization of human immunodeficiency virus type-1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus-receptor binding, and interference with events after binding, such as virus-cell membrane fusion. Here we show, by the use of a novel virus-...
Gespeichert in:
| Veröffentlicht in: | The Journal of experimental medicine 1997-10, Vol.186 (8), p.1287-1298 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1298 |
|---|---|
| container_issue | 8 |
| container_start_page | 1287 |
| container_title | The Journal of experimental medicine |
| container_volume | 186 |
| creator | Ugolini, S Mondor, I Parren, P W Burton, D R Tilley, S A Klasse, P J Sattentau, Q J |
| description | Antibody-mediated neutralization of human immunodeficiency virus type-1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus-receptor binding, and interference with events after binding, such as virus-cell membrane fusion. Here we show, by the use of a novel virus-cell binding assay, that soluble CD4 and monoclonal antibodies to all confirmed glycoprotein (gp)120 neutralizing epitopes, including the CD4 binding site and the V2 and V3 loops, inhibit the adsorption of two T cell line-adapted HIV-1 viruses to CD4+ cells. A correlation between the inhibition of virus binding and virus neutralization was observed for soluble CD4 and all anti-gp120 antibodies, indicating that this is a major mechanism of HIV neutralization. By contrast, antibodies specific for regions of gp120 other than the CD4 binding site showed little or no inhibition of either soluble gp120 binding to CD4+ cells or soluble CD4 binding to HIV-infected cells, implying that this effect is specific to the virion-cell interaction. However, inhibition of HIV-1 attachment to cells is not a universal mechanism of neutralization, since an anti-gp41 antibody did not inhibit virus-cell binding at neutralizing concentrations, implying activity after virus-cell binding. |
| doi_str_mv | 10.1084/jem.186.8.1287 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2199094</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>79344144</sourcerecordid><originalsourceid>FETCH-LOGICAL-c385t-87c476001a7eb755c408d543adbb25e0c08d1092b435eac9bbf222c0dd70851e3</originalsourceid><addsrcrecordid>eNpVkc1rGzEQxUVJSR23194KOuUSdqtPr_YSCE4TGwK5JL0KrXZsy-yuXElrSP_6ahtj2pMQ8-bNm_kh9JWSkhIlvu-hL6lalKqkTFUf0IxKQYpacnWBZoQwVlBCqk_oKsY9IVQIubhElzXngi_UDKX1sHONS84P2G_w0YUxYpOSsbsehoSTx8t7cYOTCVtI2ELXReyyBPdm7wPuwe7M4GI_db_8rePODVCY1hwStHi1_llQPMCYguncbzNN-ow-bkwX4cvpnaPXhx8vy1Xx9Py4Xt49FZYrmQpVWVEtcmhTQVNJaQVRrRTctE3DJBCbv5TUrBFcgrF102wYY5a0bUWUpMDn6Pbd9zA2PbQ2L5RD6ENwvQlv2hun_68Mbqe3_qgZrWtSi2xwfTII_tcIMenexWlHM4Afo65qLkS-aRaW70IbfIwBNuchlOiJk86cdOaklZ445YZv_0Y7y09g-B8yi4_1</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>79344144</pqid></control><display><type>article</type><title>Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Ugolini, S ; Mondor, I ; Parren, P W ; Burton, D R ; Tilley, S A ; Klasse, P J ; Sattentau, Q J</creator><creatorcontrib>Ugolini, S ; Mondor, I ; Parren, P W ; Burton, D R ; Tilley, S A ; Klasse, P J ; Sattentau, Q J</creatorcontrib><description>Antibody-mediated neutralization of human immunodeficiency virus type-1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus-receptor binding, and interference with events after binding, such as virus-cell membrane fusion. Here we show, by the use of a novel virus-cell binding assay, that soluble CD4 and monoclonal antibodies to all confirmed glycoprotein (gp)120 neutralizing epitopes, including the CD4 binding site and the V2 and V3 loops, inhibit the adsorption of two T cell line-adapted HIV-1 viruses to CD4+ cells. A correlation between the inhibition of virus binding and virus neutralization was observed for soluble CD4 and all anti-gp120 antibodies, indicating that this is a major mechanism of HIV neutralization. By contrast, antibodies specific for regions of gp120 other than the CD4 binding site showed little or no inhibition of either soluble gp120 binding to CD4+ cells or soluble CD4 binding to HIV-infected cells, implying that this effect is specific to the virion-cell interaction. However, inhibition of HIV-1 attachment to cells is not a universal mechanism of neutralization, since an anti-gp41 antibody did not inhibit virus-cell binding at neutralizing concentrations, implying activity after virus-cell binding.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.186.8.1287</identifier><identifier>PMID: 9334368</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>AIDS/HIV ; Antibodies, Blocking - pharmacology ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - pharmacology ; Antibodies, Viral - pharmacology ; CD4 Antigens - immunology ; CD4-Positive T-Lymphocytes - chemistry ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - virology ; Cell Line ; HIV Envelope Protein gp120 - immunology ; HIV Envelope Protein gp120 - metabolism ; HIV Infections - immunology ; HIV-1 - chemistry ; HIV-1 - immunology ; HIV-1 - metabolism ; HLA-DR Antigens - immunology ; Humans ; Neutralization Tests ; Receptors, Virus - antagonists & inhibitors ; Receptors, Virus - chemistry ; Solubility</subject><ispartof>The Journal of experimental medicine, 1997-10, Vol.186 (8), p.1287-1298</ispartof><rights>1997</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-87c476001a7eb755c408d543adbb25e0c08d1092b435eac9bbf222c0dd70851e3</citedby><cites>FETCH-LOGICAL-c385t-87c476001a7eb755c408d543adbb25e0c08d1092b435eac9bbf222c0dd70851e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9334368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ugolini, S</creatorcontrib><creatorcontrib>Mondor, I</creatorcontrib><creatorcontrib>Parren, P W</creatorcontrib><creatorcontrib>Burton, D R</creatorcontrib><creatorcontrib>Tilley, S A</creatorcontrib><creatorcontrib>Klasse, P J</creatorcontrib><creatorcontrib>Sattentau, Q J</creatorcontrib><title>Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Antibody-mediated neutralization of human immunodeficiency virus type-1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus-receptor binding, and interference with events after binding, such as virus-cell membrane fusion. Here we show, by the use of a novel virus-cell binding assay, that soluble CD4 and monoclonal antibodies to all confirmed glycoprotein (gp)120 neutralizing epitopes, including the CD4 binding site and the V2 and V3 loops, inhibit the adsorption of two T cell line-adapted HIV-1 viruses to CD4+ cells. A correlation between the inhibition of virus binding and virus neutralization was observed for soluble CD4 and all anti-gp120 antibodies, indicating that this is a major mechanism of HIV neutralization. By contrast, antibodies specific for regions of gp120 other than the CD4 binding site showed little or no inhibition of either soluble gp120 binding to CD4+ cells or soluble CD4 binding to HIV-infected cells, implying that this effect is specific to the virion-cell interaction. However, inhibition of HIV-1 attachment to cells is not a universal mechanism of neutralization, since an anti-gp41 antibody did not inhibit virus-cell binding at neutralizing concentrations, implying activity after virus-cell binding.</description><subject>AIDS/HIV</subject><subject>Antibodies, Blocking - pharmacology</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Viral - pharmacology</subject><subject>CD4 Antigens - immunology</subject><subject>CD4-Positive T-Lymphocytes - chemistry</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - virology</subject><subject>Cell Line</subject><subject>HIV Envelope Protein gp120 - immunology</subject><subject>HIV Envelope Protein gp120 - metabolism</subject><subject>HIV Infections - immunology</subject><subject>HIV-1 - chemistry</subject><subject>HIV-1 - immunology</subject><subject>HIV-1 - metabolism</subject><subject>HLA-DR Antigens - immunology</subject><subject>Humans</subject><subject>Neutralization Tests</subject><subject>Receptors, Virus - antagonists & inhibitors</subject><subject>Receptors, Virus - chemistry</subject><subject>Solubility</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1rGzEQxUVJSR23194KOuUSdqtPr_YSCE4TGwK5JL0KrXZsy-yuXElrSP_6ahtj2pMQ8-bNm_kh9JWSkhIlvu-hL6lalKqkTFUf0IxKQYpacnWBZoQwVlBCqk_oKsY9IVQIubhElzXngi_UDKX1sHONS84P2G_w0YUxYpOSsbsehoSTx8t7cYOTCVtI2ELXReyyBPdm7wPuwe7M4GI_db_8rePODVCY1hwStHi1_llQPMCYguncbzNN-ow-bkwX4cvpnaPXhx8vy1Xx9Py4Xt49FZYrmQpVWVEtcmhTQVNJaQVRrRTctE3DJBCbv5TUrBFcgrF102wYY5a0bUWUpMDn6Pbd9zA2PbQ2L5RD6ENwvQlv2hun_68Mbqe3_qgZrWtSi2xwfTII_tcIMenexWlHM4Afo65qLkS-aRaW70IbfIwBNuchlOiJk86cdOaklZ445YZv_0Y7y09g-B8yi4_1</recordid><startdate>19971020</startdate><enddate>19971020</enddate><creator>Ugolini, S</creator><creator>Mondor, I</creator><creator>Parren, P W</creator><creator>Burton, D R</creator><creator>Tilley, S A</creator><creator>Klasse, P J</creator><creator>Sattentau, Q J</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19971020</creationdate><title>Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization</title><author>Ugolini, S ; Mondor, I ; Parren, P W ; Burton, D R ; Tilley, S A ; Klasse, P J ; Sattentau, Q J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-87c476001a7eb755c408d543adbb25e0c08d1092b435eac9bbf222c0dd70851e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>AIDS/HIV</topic><topic>Antibodies, Blocking - pharmacology</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibodies, Viral - pharmacology</topic><topic>CD4 Antigens - immunology</topic><topic>CD4-Positive T-Lymphocytes - chemistry</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD4-Positive T-Lymphocytes - virology</topic><topic>Cell Line</topic><topic>HIV Envelope Protein gp120 - immunology</topic><topic>HIV Envelope Protein gp120 - metabolism</topic><topic>HIV Infections - immunology</topic><topic>HIV-1 - chemistry</topic><topic>HIV-1 - immunology</topic><topic>HIV-1 - metabolism</topic><topic>HLA-DR Antigens - immunology</topic><topic>Humans</topic><topic>Neutralization Tests</topic><topic>Receptors, Virus - antagonists & inhibitors</topic><topic>Receptors, Virus - chemistry</topic><topic>Solubility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ugolini, S</creatorcontrib><creatorcontrib>Mondor, I</creatorcontrib><creatorcontrib>Parren, P W</creatorcontrib><creatorcontrib>Burton, D R</creatorcontrib><creatorcontrib>Tilley, S A</creatorcontrib><creatorcontrib>Klasse, P J</creatorcontrib><creatorcontrib>Sattentau, Q J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ugolini, S</au><au>Mondor, I</au><au>Parren, P W</au><au>Burton, D R</au><au>Tilley, S A</au><au>Klasse, P J</au><au>Sattentau, Q J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>1997-10-20</date><risdate>1997</risdate><volume>186</volume><issue>8</issue><spage>1287</spage><epage>1298</epage><pages>1287-1298</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Antibody-mediated neutralization of human immunodeficiency virus type-1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus-receptor binding, and interference with events after binding, such as virus-cell membrane fusion. Here we show, by the use of a novel virus-cell binding assay, that soluble CD4 and monoclonal antibodies to all confirmed glycoprotein (gp)120 neutralizing epitopes, including the CD4 binding site and the V2 and V3 loops, inhibit the adsorption of two T cell line-adapted HIV-1 viruses to CD4+ cells. A correlation between the inhibition of virus binding and virus neutralization was observed for soluble CD4 and all anti-gp120 antibodies, indicating that this is a major mechanism of HIV neutralization. By contrast, antibodies specific for regions of gp120 other than the CD4 binding site showed little or no inhibition of either soluble gp120 binding to CD4+ cells or soluble CD4 binding to HIV-infected cells, implying that this effect is specific to the virion-cell interaction. However, inhibition of HIV-1 attachment to cells is not a universal mechanism of neutralization, since an anti-gp41 antibody did not inhibit virus-cell binding at neutralizing concentrations, implying activity after virus-cell binding.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>9334368</pmid><doi>10.1084/jem.186.8.1287</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1007 |
| ispartof | The Journal of experimental medicine, 1997-10, Vol.186 (8), p.1287-1298 |
| issn | 0022-1007 1540-9538 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2199094 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | AIDS/HIV Antibodies, Blocking - pharmacology Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - pharmacology Antibodies, Viral - pharmacology CD4 Antigens - immunology CD4-Positive T-Lymphocytes - chemistry CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - virology Cell Line HIV Envelope Protein gp120 - immunology HIV Envelope Protein gp120 - metabolism HIV Infections - immunology HIV-1 - chemistry HIV-1 - immunology HIV-1 - metabolism HLA-DR Antigens - immunology Humans Neutralization Tests Receptors, Virus - antagonists & inhibitors Receptors, Virus - chemistry Solubility |
| title | Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T00%3A24%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20virus%20attachment%20to%20CD4+%20target%20cells%20is%20a%20major%20mechanism%20of%20T%20cell%20line-adapted%20HIV-1%20neutralization&rft.jtitle=The%20Journal%20of%20experimental%20medicine&rft.au=Ugolini,%20S&rft.date=1997-10-20&rft.volume=186&rft.issue=8&rft.spage=1287&rft.epage=1298&rft.pages=1287-1298&rft.issn=0022-1007&rft.eissn=1540-9538&rft_id=info:doi/10.1084/jem.186.8.1287&rft_dat=%3Cproquest_pubme%3E79344144%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=79344144&rft_id=info:pmid/9334368&rfr_iscdi=true |