Infrequent Recovery of HIV from but Robust Exogenous Infection of Activated CD4+ T Cells in HIV Elite Controllers
Background. Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV-1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected periph...
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| Veröffentlicht in: | Clinical infectious diseases 2010-07, Vol.51 (2), p.233-238 |
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| creator | Julg, B. Pereyra, F. Buzón, M. J. Piechocka-Trocha, A. Clark, M. J. Baker, B. M. Lian, J. Miura, T. Martinez-Picado, J. Addo, M. M. Walker, B. D. |
| description | Background. Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV-1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected peripheral CD4+ T cells have been reported in this group, it remains unclear to what extent these are due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication. Methods. We assessed proviral DNA levels, autologous viral growth from and infectability of in vitro activated, CD8+ T cell—depleted CD4+ T cells from HIV elite controllers (mean viral load, |
| doi_str_mv | 10.1086/653677 |
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J. ; Piechocka-Trocha, A. ; Clark, M. J. ; Baker, B. M. ; Lian, J. ; Miura, T. ; Martinez-Picado, J. ; Addo, M. M. ; Walker, B. D.</creator><creatorcontrib>Julg, B. ; Pereyra, F. ; Buzón, M. J. ; Piechocka-Trocha, A. ; Clark, M. J. ; Baker, B. M. ; Lian, J. ; Miura, T. ; Martinez-Picado, J. ; Addo, M. M. ; Walker, B. D.</creatorcontrib><description>Background. Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV-1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected peripheral CD4+ T cells have been reported in this group, it remains unclear to what extent these are due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication. Methods. We assessed proviral DNA levels, autologous viral growth from and infectability of in vitro activated, CD8+ T cell—depleted CD4+ T cells from HIV elite controllers (mean viral load, <50 copies/mL), viremic controllers (mean viral load, <2000 copies/mL), chronic progressors, and individuals receiving highly active antiretroviral therapy. Results. Although we successfully detected autologous virus production in ex vivo activated CD4+ T cells from all chronic progressors and from most of the viremic controllers, we were able to measure robust autologous viral replication in only 2 of 14 elite controllers subjected to the same protocol. In vitro activated autologous CD4+ T cells from elite controllers, however, supported infection with both X4 and R5 tropic HIV strains at comparable levels to those in CD4+ T cells from HIV-uninfected subjects. Proviral DNA levels were the lowest in elite controllers, suggesting that extremely low frequencies of infected cells contribute to difficulty in isolation of virus. Conclusions. These data indicate that elite control is not due to inability of activated CD4+ T cells to support HIV infection, but the relative contributions of host and viral factors that account for maintenance of low-level infection remain to be determined.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1086/653677</identifier><identifier>PMID: 20550452</identifier><identifier>CODEN: CIDIEL</identifier><language>eng</language><publisher>Oxford: The University of Chicago Press</publisher><subject>Antiretroviral drugs ; Biological and medical sciences ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - virology ; Cells, Cultured ; Cultured cells ; Deoxyribonucleic acid ; DNA ; Elites ; Genotype & phenotype ; Highly active antiretroviral therapy ; HIV ; HIV 1 ; HIV Infections - immunology ; HIV Infections - virology ; HIV Long-Term Survivors ; HIV-1 - immunology ; HIV-1 - pathogenicity ; HIV/AIDS ; HLA antigens ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infections ; Infectious diseases ; Medical sciences ; RNA ; T cell receptors ; T lymphocytes ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Virulence ; Virus Replication ; Viruses</subject><ispartof>Clinical infectious diseases, 2010-07, Vol.51 (2), p.233-238</ispartof><rights>2010 Infectious Diseases Society of America</rights><rights>2010 by the Infectious Diseases Society of America 2010</rights><rights>2015 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Jul 15, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-b22d0f758a46dacd534b042fdbc6a94b745dd48c10e273e1769c9cfe3980dc913</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25680001$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25680001$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22995148$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20550452$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Julg, B.</creatorcontrib><creatorcontrib>Pereyra, F.</creatorcontrib><creatorcontrib>Buzón, M. J.</creatorcontrib><creatorcontrib>Piechocka-Trocha, A.</creatorcontrib><creatorcontrib>Clark, M. J.</creatorcontrib><creatorcontrib>Baker, B. M.</creatorcontrib><creatorcontrib>Lian, J.</creatorcontrib><creatorcontrib>Miura, T.</creatorcontrib><creatorcontrib>Martinez-Picado, J.</creatorcontrib><creatorcontrib>Addo, M. M.</creatorcontrib><creatorcontrib>Walker, B. D.</creatorcontrib><title>Infrequent Recovery of HIV from but Robust Exogenous Infection of Activated CD4+ T Cells in HIV Elite Controllers</title><title>Clinical infectious diseases</title><addtitle>Clinical Infectious Diseases</addtitle><addtitle>Clinical Infectious Diseases</addtitle><description>Background. Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV-1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected peripheral CD4+ T cells have been reported in this group, it remains unclear to what extent these are due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication. Methods. We assessed proviral DNA levels, autologous viral growth from and infectability of in vitro activated, CD8+ T cell—depleted CD4+ T cells from HIV elite controllers (mean viral load, <50 copies/mL), viremic controllers (mean viral load, <2000 copies/mL), chronic progressors, and individuals receiving highly active antiretroviral therapy. Results. Although we successfully detected autologous virus production in ex vivo activated CD4+ T cells from all chronic progressors and from most of the viremic controllers, we were able to measure robust autologous viral replication in only 2 of 14 elite controllers subjected to the same protocol. In vitro activated autologous CD4+ T cells from elite controllers, however, supported infection with both X4 and R5 tropic HIV strains at comparable levels to those in CD4+ T cells from HIV-uninfected subjects. Proviral DNA levels were the lowest in elite controllers, suggesting that extremely low frequencies of infected cells contribute to difficulty in isolation of virus. Conclusions. These data indicate that elite control is not due to inability of activated CD4+ T cells to support HIV infection, but the relative contributions of host and viral factors that account for maintenance of low-level infection remain to be determined.</description><subject>Antiretroviral drugs</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - virology</subject><subject>Cells, Cultured</subject><subject>Cultured cells</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Elites</subject><subject>Genotype & phenotype</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV 1</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>HIV Long-Term Survivors</subject><subject>HIV-1 - immunology</subject><subject>HIV-1 - pathogenicity</subject><subject>HIV/AIDS</subject><subject>HLA antigens</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>RNA</subject><subject>T cell receptors</subject><subject>T lymphocytes</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Virulence</subject><subject>Virus Replication</subject><subject>Viruses</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkl9rFDEUxQdRbK36DZQoqA8ymkySSfJYpqu7sq1QahFfQiZ_ZLazk22SKe23N9tZWxCkecmF88tJzr0pipcIfkKQ159rimvGHhX7iGJW1lSgx7mGlJeEY75XPItxBSFCHNKnxV4FKYWEVvvF5WJwwV6Odkjg1Gp_ZcMN8A7MF-fABb8G7ZgF344xgdm1_20HP0aQD1mdOj9s0cNcXalkDWiOyEdwBhrb9xF0w63JrO-SBY0fUvB9b0N8Xjxxqo_2xW4_KH58mZ0183L5_euiOVyWmnCayraqDHSMckVqo7ShmLSQVM60ulaCtIxQYwjXCNqKYYtYLbTQzmLBodEC4YPiw-S7CT7ni0muu6jz09RgcwbJOUeIioo_SDKcV26lyOTbf8iVH8OQY0jKOMldJzBD7ydIBx9jsE5uQrdW4UYiKLfDktOwMvh65za2a2vusL_TycC7HaCiVr0LatBdvOcqISgi2wBvJs6Pm_9f9mpiVjH5cO9Baw7zx8h6OeldTPb6TlfhQtYMMyrnP3_J5bdzenxyWskj_Aefhbv-</recordid><startdate>20100715</startdate><enddate>20100715</enddate><creator>Julg, B.</creator><creator>Pereyra, F.</creator><creator>Buzón, M. 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D.</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QL</scope><scope>7T2</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>7U2</scope></search><sort><creationdate>20100715</creationdate><title>Infrequent Recovery of HIV from but Robust Exogenous Infection of Activated CD4+ T Cells in HIV Elite Controllers</title><author>Julg, B. ; Pereyra, F. ; Buzón, M. J. ; Piechocka-Trocha, A. ; Clark, M. J. ; Baker, B. M. ; Lian, J. ; Miura, T. ; Martinez-Picado, J. ; Addo, M. M. ; Walker, B. 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Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>RNA</topic><topic>T cell receptors</topic><topic>T lymphocytes</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Virulence</topic><topic>Virus Replication</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Julg, B.</creatorcontrib><creatorcontrib>Pereyra, F.</creatorcontrib><creatorcontrib>Buzón, M. J.</creatorcontrib><creatorcontrib>Piechocka-Trocha, A.</creatorcontrib><creatorcontrib>Clark, M. J.</creatorcontrib><creatorcontrib>Baker, B. M.</creatorcontrib><creatorcontrib>Lian, J.</creatorcontrib><creatorcontrib>Miura, T.</creatorcontrib><creatorcontrib>Martinez-Picado, J.</creatorcontrib><creatorcontrib>Addo, M. M.</creatorcontrib><creatorcontrib>Walker, B. 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J.</au><au>Piechocka-Trocha, A.</au><au>Clark, M. J.</au><au>Baker, B. M.</au><au>Lian, J.</au><au>Miura, T.</au><au>Martinez-Picado, J.</au><au>Addo, M. M.</au><au>Walker, B. D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Infrequent Recovery of HIV from but Robust Exogenous Infection of Activated CD4+ T Cells in HIV Elite Controllers</atitle><jtitle>Clinical infectious diseases</jtitle><stitle>Clinical Infectious Diseases</stitle><addtitle>Clinical Infectious Diseases</addtitle><date>2010-07-15</date><risdate>2010</risdate><volume>51</volume><issue>2</issue><spage>233</spage><epage>238</epage><pages>233-238</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><coden>CIDIEL</coden><abstract>Background. Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV-1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected peripheral CD4+ T cells have been reported in this group, it remains unclear to what extent these are due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication. Methods. We assessed proviral DNA levels, autologous viral growth from and infectability of in vitro activated, CD8+ T cell—depleted CD4+ T cells from HIV elite controllers (mean viral load, <50 copies/mL), viremic controllers (mean viral load, <2000 copies/mL), chronic progressors, and individuals receiving highly active antiretroviral therapy. Results. Although we successfully detected autologous virus production in ex vivo activated CD4+ T cells from all chronic progressors and from most of the viremic controllers, we were able to measure robust autologous viral replication in only 2 of 14 elite controllers subjected to the same protocol. In vitro activated autologous CD4+ T cells from elite controllers, however, supported infection with both X4 and R5 tropic HIV strains at comparable levels to those in CD4+ T cells from HIV-uninfected subjects. Proviral DNA levels were the lowest in elite controllers, suggesting that extremely low frequencies of infected cells contribute to difficulty in isolation of virus. Conclusions. These data indicate that elite control is not due to inability of activated CD4+ T cells to support HIV infection, but the relative contributions of host and viral factors that account for maintenance of low-level infection remain to be determined.</abstract><cop>Oxford</cop><pub>The University of Chicago Press</pub><pmid>20550452</pmid><doi>10.1086/653677</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Antiretroviral drugs Biological and medical sciences CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - virology Cells, Cultured Cultured cells Deoxyribonucleic acid DNA Elites Genotype & phenotype Highly active antiretroviral therapy HIV HIV 1 HIV Infections - immunology HIV Infections - virology HIV Long-Term Survivors HIV-1 - immunology HIV-1 - pathogenicity HIV/AIDS HLA antigens Human immunodeficiency virus Human immunodeficiency virus 1 Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infections Infectious diseases Medical sciences RNA T cell receptors T lymphocytes Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Virulence Virus Replication Viruses |
| title | Infrequent Recovery of HIV from but Robust Exogenous Infection of Activated CD4+ T Cells in HIV Elite Controllers |
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