Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo
The majority of HIV-1 infections in women occur through vaginal intercourse, in which virus-containing semen is deposited on the cervico-vaginal mucosa. Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission....
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| Veröffentlicht in: | PLoS pathogens 2013-02, Vol.9 (2), p.e1003148-e1003148 |
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| description | The majority of HIV-1 infections in women occur through vaginal intercourse, in which virus-containing semen is deposited on the cervico-vaginal mucosa. Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission. The concentration of interleukin (IL)-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. We simulated an in vivo situation by depositing HIV-1 on cervico-vaginal tissue in combination with IL-7 at concentrations comparable with those measured in semen of HIV-1-infected individuals. We found that IL-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, we observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4⁺ T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma (Bcl)-2. Also, IL-7 increased the fraction of cycling CD4⁺ T cells, as evidenced by staining for the nuclear factor Ki-67. High levels of seminal IL-7 in vivo may be relevant to the survival of the founder pool of HIV-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection, promoting local expansion and dissemination of HIV infection. |
| doi_str_mv | 10.1371/journal.ppat.1003148 |
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Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission. The concentration of interleukin (IL)-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. We simulated an in vivo situation by depositing HIV-1 on cervico-vaginal tissue in combination with IL-7 at concentrations comparable with those measured in semen of HIV-1-infected individuals. We found that IL-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, we observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4⁺ T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma (Bcl)-2. Also, IL-7 increased the fraction of cycling CD4⁺ T cells, as evidenced by staining for the nuclear factor Ki-67. High levels of seminal IL-7 in vivo may be relevant to the survival of the founder pool of HIV-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection, promoting local expansion and dissemination of HIV infection.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1003148</identifier><identifier>PMID: 23408885</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; Apoptosis ; Apoptosis Regulatory Proteins - metabolism ; Biology ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - virology ; Cell Proliferation ; Cervix Uteri - virology ; Colleges & universities ; Disease transmission ; Experiments ; Female ; Gene Expression Regulation, Viral ; Health aspects ; HIV ; HIV infection ; HIV Infections - transmission ; HIV Infections - virology ; HIV-1 - physiology ; Human immunodeficiency virus ; Humans ; Interleukin-7 - metabolism ; Interleukins ; Ki-67 Antigen - metabolism ; Lymphocytes ; Lymphoid Tissue - virology ; Male ; Medicine ; Molecular Sequence Data ; Palatine Tonsil - virology ; Physiological aspects ; Plasma ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Recombinant Proteins ; Sexual intercourse ; Statistical analysis ; Vagina - virology ; Virus Replication</subject><ispartof>PLoS pathogens, 2013-02, Vol.9 (2), p.e1003148-e1003148</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Introini A, Vanpouille C, Lisco A, Grivel J-C, Margolis L (2013) Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue ex vivo. PLoS Pathog 9(2): e1003148. doi:10.1371/journal.ppat.1003148</rights><rights>2013</rights><rights>2013 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Introini A, Vanpouille C, Lisco A, Grivel J-C, Margolis L (2013) Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue ex vivo. PLoS Pathog 9(2): e1003148. doi:10.1371/journal.ppat.1003148</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c661t-c290ec41caaaaceb4cfc7a23cb47f4fc0a46fe23c335ffc6f1f6fa4bd13c663c3</citedby><cites>FETCH-LOGICAL-c661t-c290ec41caaaaceb4cfc7a23cb47f4fc0a46fe23c335ffc6f1f6fa4bd13c663c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567179/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567179/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23408885$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ross, Susan R.</contributor><creatorcontrib>Introini, Andrea</creatorcontrib><creatorcontrib>Vanpouille, Christophe</creatorcontrib><creatorcontrib>Lisco, Andrea</creatorcontrib><creatorcontrib>Grivel, Jean-Charles</creatorcontrib><creatorcontrib>Margolis, Leonid</creatorcontrib><title>Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>The majority of HIV-1 infections in women occur through vaginal intercourse, in which virus-containing semen is deposited on the cervico-vaginal mucosa. Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission. The concentration of interleukin (IL)-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. We simulated an in vivo situation by depositing HIV-1 on cervico-vaginal tissue in combination with IL-7 at concentrations comparable with those measured in semen of HIV-1-infected individuals. We found that IL-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, we observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4⁺ T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma (Bcl)-2. Also, IL-7 increased the fraction of cycling CD4⁺ T cells, as evidenced by staining for the nuclear factor Ki-67. High levels of seminal IL-7 in vivo may be relevant to the survival of the founder pool of HIV-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection, promoting local expansion and dissemination of HIV infection.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Biology</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - virology</subject><subject>Cell Proliferation</subject><subject>Cervix Uteri - virology</subject><subject>Colleges & universities</subject><subject>Disease transmission</subject><subject>Experiments</subject><subject>Female</subject><subject>Gene Expression Regulation, Viral</subject><subject>Health aspects</subject><subject>HIV</subject><subject>HIV infection</subject><subject>HIV Infections - transmission</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Interleukin-7 - metabolism</subject><subject>Interleukins</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Lymphocytes</subject><subject>Lymphoid Tissue - virology</subject><subject>Male</subject><subject>Medicine</subject><subject>Molecular Sequence Data</subject><subject>Palatine Tonsil - virology</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Recombinant Proteins</subject><subject>Sexual intercourse</subject><subject>Statistical analysis</subject><subject>Vagina - virology</subject><subject>Virus Replication</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVkk1v1DAQhiMEoqXwDxBE4gKHLHHsfOwFqaqARqqKxNfVmjjj4CUbb20nKv-e2W5aNagX4kOS8TPveF5PFL1k6Yrxkr3f2NEN0K92OwgrlqaciepRdMzynCclL8Xje99H0TPvN2kqGGfF0-go4yKtqio_ji7rIaDrcfxthqSMNSjTmwABfXxe_0xYHBwMfmu8N3aIg40Vuskom0zQGSofB9oaMcbreDKTfR490dB7fDG_T6Ifnz5-PztPLr58rs9OLxJVFCwkKlunqARTQI_CRiitSsi4akSphVYpiEIj_XOea60KzXShQTQt4yRA4ZPo9UF311svZyu8pPYEF6LMCiLqA9Fa2MidM1twf6QFI28C1nUSXDCqR8kFo3IlCmCFyNL1umJtm4mGixwyUA1pfZirjc0WW4UDudIvRJc7g_klOztJnhclK9ck8HYWcPZqRB8kOaqw72FAO9K5s6riLMtv0Df_oA93N1MdUANm0Jbqqr2oPOXZuqIl9tTqAYpWi1u6wwG1ofgi4d0igZiA16GD0XtZf_v6H-zlkhUHVjnrvUN95x1L5X6ab5uU-2mW8zRT2qv7vt8l3Y4v_wu9nPDq</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Introini, Andrea</creator><creator>Vanpouille, Christophe</creator><creator>Lisco, Andrea</creator><creator>Grivel, Jean-Charles</creator><creator>Margolis, Leonid</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130201</creationdate><title>Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo</title><author>Introini, Andrea ; Vanpouille, Christophe ; Lisco, Andrea ; Grivel, Jean-Charles ; Margolis, Leonid</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c661t-c290ec41caaaaceb4cfc7a23cb47f4fc0a46fe23c335ffc6f1f6fa4bd13c663c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>AIDS</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Biology</topic><topic>CD4-Positive T-Lymphocytes - cytology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD4-Positive T-Lymphocytes - virology</topic><topic>Cell Proliferation</topic><topic>Cervix Uteri - virology</topic><topic>Colleges & universities</topic><topic>Disease transmission</topic><topic>Experiments</topic><topic>Female</topic><topic>Gene Expression Regulation, Viral</topic><topic>Health aspects</topic><topic>HIV</topic><topic>HIV infection</topic><topic>HIV Infections - transmission</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - physiology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Interleukin-7 - metabolism</topic><topic>Interleukins</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Lymphocytes</topic><topic>Lymphoid Tissue - virology</topic><topic>Male</topic><topic>Medicine</topic><topic>Molecular Sequence Data</topic><topic>Palatine Tonsil - virology</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Recombinant Proteins</topic><topic>Sexual intercourse</topic><topic>Statistical analysis</topic><topic>Vagina - virology</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Introini, Andrea</creatorcontrib><creatorcontrib>Vanpouille, Christophe</creatorcontrib><creatorcontrib>Lisco, Andrea</creatorcontrib><creatorcontrib>Grivel, Jean-Charles</creatorcontrib><creatorcontrib>Margolis, Leonid</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Introini, Andrea</au><au>Vanpouille, Christophe</au><au>Lisco, Andrea</au><au>Grivel, Jean-Charles</au><au>Margolis, Leonid</au><au>Ross, Susan R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>9</volume><issue>2</issue><spage>e1003148</spage><epage>e1003148</epage><pages>e1003148-e1003148</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>The majority of HIV-1 infections in women occur through vaginal intercourse, in which virus-containing semen is deposited on the cervico-vaginal mucosa. Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission. The concentration of interleukin (IL)-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. We simulated an in vivo situation by depositing HIV-1 on cervico-vaginal tissue in combination with IL-7 at concentrations comparable with those measured in semen of HIV-1-infected individuals. We found that IL-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, we observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4⁺ T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma (Bcl)-2. Also, IL-7 increased the fraction of cycling CD4⁺ T cells, as evidenced by staining for the nuclear factor Ki-67. High levels of seminal IL-7 in vivo may be relevant to the survival of the founder pool of HIV-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection, promoting local expansion and dissemination of HIV infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23408885</pmid><doi>10.1371/journal.ppat.1003148</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Acquired immune deficiency syndrome AIDS Apoptosis Apoptosis Regulatory Proteins - metabolism Biology CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - virology Cell Proliferation Cervix Uteri - virology Colleges & universities Disease transmission Experiments Female Gene Expression Regulation, Viral Health aspects HIV HIV infection HIV Infections - transmission HIV Infections - virology HIV-1 - physiology Human immunodeficiency virus Humans Interleukin-7 - metabolism Interleukins Ki-67 Antigen - metabolism Lymphocytes Lymphoid Tissue - virology Male Medicine Molecular Sequence Data Palatine Tonsil - virology Physiological aspects Plasma Proteins Proto-Oncogene Proteins c-bcl-2 - metabolism Recombinant Proteins Sexual intercourse Statistical analysis Vagina - virology Virus Replication |
| title | Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo |
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