Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques
Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non-AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 admi...
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| Veröffentlicht in: | The Journal of clinical investigation 2015-12, Vol.125 (12), p.4497-4513 |
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| creator | Micci, Luca Ryan, Emily S Fromentin, Rémi Bosinger, Steven E Harper, Justin L He, Tianyu Paganini, Sara Easley, Kirk A Chahroudi, Ann Benne, Clarisse Gumber, Sanjeev McGary, Colleen S Rogers, Kenneth A Deleage, Claire Lucero, Carissa Byrareddy, Siddappa N Apetrei, Cristian Estes, Jacob D Lifson, Jeffrey D Piatak, Jr, Michael Chomont, Nicolas Villinger, Francois Silvestri, Guido Brenchley, Jason M Paiardini, Mirko |
| description | Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non-AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4(+) T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21-treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection. |
| doi_str_mv | 10.1172/JCI81400 |
| format | Article |
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Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4(+) T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21-treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection.</description><identifier>ISSN: 0021-9738</identifier><identifier>ISSN: 1558-8238</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI81400</identifier><identifier>PMID: 26551680</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; Animals ; Anti-Retroviral Agents - pharmacology ; Antiretroviral drugs ; Antiviral agents ; Biomedical research ; Care and treatment ; DNA, Viral - blood ; DNA, Viral - immunology ; Dosage and administration ; Drug therapy ; Health aspects ; HIV ; HIV infection ; Human immunodeficiency virus ; Infections ; Inflammation ; Inflammation - blood ; Inflammation - drug therapy ; Inflammation - immunology ; Inflammation - pathology ; Inflammation - virology ; Interleukin-21 ; Interleukins - pharmacology ; Intestinal Mucosa - metabolism ; Intestines - immunology ; Intestines - pathology ; Intestines - virology ; Laboratory animals ; Lymphocytes ; Macaca mulatta ; Measurement ; RNA, Viral - blood ; RNA, Viral - immunology ; Simian Acquired Immunodeficiency Syndrome - blood ; Simian Acquired Immunodeficiency Syndrome - drug therapy ; Simian Acquired Immunodeficiency Syndrome - immunology ; Simian Acquired Immunodeficiency Syndrome - pathology ; Simian immunodeficiency virus ; Simian Immunodeficiency Virus - immunology ; Simian Immunodeficiency Virus - metabolism ; Swine influenza virus ; Th17 Cells - immunology ; Th17 Cells - metabolism ; Th17 Cells - pathology ; Time Factors ; Viremia</subject><ispartof>The Journal of clinical investigation, 2015-12, Vol.125 (12), p.4497-4513</ispartof><rights>COPYRIGHT 2015 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Dec 2015</rights><rights>Copyright © 2015, American Society for Clinical Investigation 2015 American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c637t-2e34c7bd1f4feacd0bce9776be7d1164b9530605fa832f81a727cc3ffa65b81a3</citedby><cites>FETCH-LOGICAL-c637t-2e34c7bd1f4feacd0bce9776be7d1164b9530605fa832f81a727cc3ffa65b81a3</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/PMC4665780/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665780/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26551680$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Micci, Luca</creatorcontrib><creatorcontrib>Ryan, Emily S</creatorcontrib><creatorcontrib>Fromentin, Rémi</creatorcontrib><creatorcontrib>Bosinger, Steven E</creatorcontrib><creatorcontrib>Harper, Justin L</creatorcontrib><creatorcontrib>He, Tianyu</creatorcontrib><creatorcontrib>Paganini, Sara</creatorcontrib><creatorcontrib>Easley, Kirk A</creatorcontrib><creatorcontrib>Chahroudi, Ann</creatorcontrib><creatorcontrib>Benne, Clarisse</creatorcontrib><creatorcontrib>Gumber, Sanjeev</creatorcontrib><creatorcontrib>McGary, Colleen S</creatorcontrib><creatorcontrib>Rogers, Kenneth A</creatorcontrib><creatorcontrib>Deleage, Claire</creatorcontrib><creatorcontrib>Lucero, Carissa</creatorcontrib><creatorcontrib>Byrareddy, Siddappa N</creatorcontrib><creatorcontrib>Apetrei, Cristian</creatorcontrib><creatorcontrib>Estes, Jacob D</creatorcontrib><creatorcontrib>Lifson, Jeffrey D</creatorcontrib><creatorcontrib>Piatak, Jr, Michael</creatorcontrib><creatorcontrib>Chomont, Nicolas</creatorcontrib><creatorcontrib>Villinger, Francois</creatorcontrib><creatorcontrib>Silvestri, Guido</creatorcontrib><creatorcontrib>Brenchley, Jason M</creatorcontrib><creatorcontrib>Paiardini, Mirko</creatorcontrib><title>Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non-AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4(+) T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21-treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>Animals</subject><subject>Anti-Retroviral Agents - pharmacology</subject><subject>Antiretroviral drugs</subject><subject>Antiviral agents</subject><subject>Biomedical research</subject><subject>Care and treatment</subject><subject>DNA, Viral - blood</subject><subject>DNA, Viral - immunology</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Health aspects</subject><subject>HIV</subject><subject>HIV infection</subject><subject>Human immunodeficiency virus</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Inflammation - blood</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - immunology</subject><subject>Inflammation - pathology</subject><subject>Inflammation - virology</subject><subject>Interleukin-21</subject><subject>Interleukins - pharmacology</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestines - immunology</subject><subject>Intestines - pathology</subject><subject>Intestines - virology</subject><subject>Laboratory animals</subject><subject>Lymphocytes</subject><subject>Macaca mulatta</subject><subject>Measurement</subject><subject>RNA, Viral - blood</subject><subject>RNA, Viral - immunology</subject><subject>Simian Acquired Immunodeficiency Syndrome - blood</subject><subject>Simian Acquired Immunodeficiency Syndrome - drug therapy</subject><subject>Simian Acquired Immunodeficiency Syndrome - immunology</subject><subject>Simian Acquired Immunodeficiency Syndrome - pathology</subject><subject>Simian immunodeficiency virus</subject><subject>Simian Immunodeficiency Virus - immunology</subject><subject>Simian Immunodeficiency Virus - 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Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4(+) T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21-treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>26551680</pmid><doi>10.1172/JCI81400</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of clinical investigation, 2015-12, Vol.125 (12), p.4497-4513 |
| issn | 0021-9738 1558-8238 1558-8238 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4665780 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Journals@Ovid Complete |
| subjects | Acquired immune deficiency syndrome AIDS Animals Anti-Retroviral Agents - pharmacology Antiretroviral drugs Antiviral agents Biomedical research Care and treatment DNA, Viral - blood DNA, Viral - immunology Dosage and administration Drug therapy Health aspects HIV HIV infection Human immunodeficiency virus Infections Inflammation Inflammation - blood Inflammation - drug therapy Inflammation - immunology Inflammation - pathology Inflammation - virology Interleukin-21 Interleukins - pharmacology Intestinal Mucosa - metabolism Intestines - immunology Intestines - pathology Intestines - virology Laboratory animals Lymphocytes Macaca mulatta Measurement RNA, Viral - blood RNA, Viral - immunology Simian Acquired Immunodeficiency Syndrome - blood Simian Acquired Immunodeficiency Syndrome - drug therapy Simian Acquired Immunodeficiency Syndrome - immunology Simian Acquired Immunodeficiency Syndrome - pathology Simian immunodeficiency virus Simian Immunodeficiency Virus - immunology Simian Immunodeficiency Virus - metabolism Swine influenza virus Th17 Cells - immunology Th17 Cells - metabolism Th17 Cells - pathology Time Factors Viremia |
| title | Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T16%3A30%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interleukin-21%20combined%20with%20ART%20reduces%20inflammation%20and%20viral%20reservoir%20in%20SIV-infected%20macaques&rft.jtitle=The%20Journal%20of%20clinical%20investigation&rft.au=Micci,%20Luca&rft.date=2015-12-01&rft.volume=125&rft.issue=12&rft.spage=4497&rft.epage=4513&rft.pages=4497-4513&rft.issn=0021-9738&rft.eissn=1558-8238&rft_id=info:doi/10.1172/JCI81400&rft_dat=%3Cgale_pubme%3EA436234490%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1746922491&rft_id=info:pmid/26551680&rft_galeid=A436234490&rfr_iscdi=true |