Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression
Type I interferon (IFNα/β) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNα/β plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNα/β in HIV-1 infection...
Gespeichert in:
| Veröffentlicht in: | Blood 2009-05, Vol.113 (22), p.5497-5505 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5505 |
|---|---|
| container_issue | 22 |
| container_start_page | 5497 |
| container_title | Blood |
| container_volume | 113 |
| creator | Hardy, Gareth A.D. Sieg, Scott F. Rodriguez, Benigno Jiang, Wei Asaad, Robert Lederman, Michael M. Harding, Clifford V. |
| description | Type I interferon (IFNα/β) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNα/β plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNα/β in HIV-1 infection is poorly understood. We report significant defects in IFNα/β receptor (IFNα/βR) expression, IFNα signaling, and IFNα-induced gene expression in monocytes from HIV-1–infected subjects. IFNα/βR expression correlated directly with CD4+ T-cell count and inversely with HIV-1 RNA level and expression of CD38 by memory (CD45RO+) CD8+ T cells, a measure of pathologic immune activation in HIV-1 infection associated with disease progression. In addition, monocytes from HIV-1–infected persons showed diminished responses to IFNα, including decreased induction of phosphorylated STAT1 and the classical interferon-stimulated gene produces MxA and OAS. These IFNα responses were decreased regardless of IFNα/βR expression, suggesting that regulation of intracellular signaling may contribute to unresponsiveness to IFNα/β in HIV-1 disease. Defective monocyte responses to IFNα/β may play an important role in the pathogenesis of HIV-1 infection, and decreased IFNα/βR expression may serve as a novel marker of disease progression. |
| doi_str_mv | 10.1182/blood-2008-11-190231 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2689050</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497120373882</els_id><sourcerecordid>67299989</sourcerecordid><originalsourceid>FETCH-LOGICAL-c491t-9c5bb4f9d6587251167b616af91f6b9ceb477d96e9c2dda18f676968e02fe7c3</originalsourceid><addsrcrecordid>eNp9kV9vFCEUxYmxsWv1GxjDi76N5bIzzPBiYuqfbtKkL42vhIFLi87ACuw2bfrhpd1Nqy99Ai7nHg73R8g7YJ8ABn48TjHahjM2NAANSMaX8IIsoONDwxhnL8mCMSaaVvZwSF7n_IsxaJe8e0UOQXIpRccW5O4rZgzZF3-ri4-BlkjLzRrpivpQMDlMtegDPV39bKBuHJoHnYkp4aQLZnrtyxWddfqNKdPoqJ_nTUCqq3C7M9XBUusz6ox0neJlwpxr_Q05cHrK-Ha_HpGL798uTk6bs_Mfq5MvZ41pJZRGmm4cWyet6IaedwCiHwUI7SQ4MUqDY9v3VgqUhlurYXCiF1IMyLjD3iyPyOed7XozzmgNhpL0pNbJ19A3Kmqv_r8J_kpdxq3iYpCsY9Xg494gxT8bzEXNPhucJh0wbrISfR2nHGQVtjuhSTHnhO7xEWDqnpp6oKbuqdWz2lGrbe__DfjUtMdUBR_2Ap2NnlzSwfj8qOPQtbIyf_op1mluPSaVjcdg0PpUuSkb_fNJ_gL9BLnn</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67299989</pqid></control><display><type>article</type><title>Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Hardy, Gareth A.D. ; Sieg, Scott F. ; Rodriguez, Benigno ; Jiang, Wei ; Asaad, Robert ; Lederman, Michael M. ; Harding, Clifford V.</creator><creatorcontrib>Hardy, Gareth A.D. ; Sieg, Scott F. ; Rodriguez, Benigno ; Jiang, Wei ; Asaad, Robert ; Lederman, Michael M. ; Harding, Clifford V.</creatorcontrib><description>Type I interferon (IFNα/β) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNα/β plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNα/β in HIV-1 infection is poorly understood. We report significant defects in IFNα/β receptor (IFNα/βR) expression, IFNα signaling, and IFNα-induced gene expression in monocytes from HIV-1–infected subjects. IFNα/βR expression correlated directly with CD4+ T-cell count and inversely with HIV-1 RNA level and expression of CD38 by memory (CD45RO+) CD8+ T cells, a measure of pathologic immune activation in HIV-1 infection associated with disease progression. In addition, monocytes from HIV-1–infected persons showed diminished responses to IFNα, including decreased induction of phosphorylated STAT1 and the classical interferon-stimulated gene produces MxA and OAS. These IFNα responses were decreased regardless of IFNα/βR expression, suggesting that regulation of intracellular signaling may contribute to unresponsiveness to IFNα/β in HIV-1 disease. Defective monocyte responses to IFNα/β may play an important role in the pathogenesis of HIV-1 infection, and decreased IFNα/βR expression may serve as a novel marker of disease progression.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2008-11-190231</identifier><identifier>PMID: 19299650</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adult ; Antiviral Agents - therapeutic use ; Biological and medical sciences ; Biomarkers - blood ; Case-Control Studies ; Cross-Sectional Studies ; Disease Progression ; Drug Resistance, Viral - immunology ; Female ; Hematologic and hematopoietic diseases ; HIV Infections - blood ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV-1 - immunology ; Human viral diseases ; Humans ; Immunity, Active - drug effects ; Immunobiology ; Infectious diseases ; Interferon Type I - therapeutic use ; Male ; Medical sciences ; Middle Aged ; Monocytes - metabolism ; Monocytes - pathology ; Receptors, Interferon - metabolism ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids</subject><ispartof>Blood, 2009-05, Vol.113 (22), p.5497-5505</ispartof><rights>2009 American Society of Hematology</rights><rights>2009 INIST-CNRS</rights><rights>2009 by The American Society of Hematology 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-9c5bb4f9d6587251167b616af91f6b9ceb477d96e9c2dda18f676968e02fe7c3</citedby><cites>FETCH-LOGICAL-c491t-9c5bb4f9d6587251167b616af91f6b9ceb477d96e9c2dda18f676968e02fe7c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21549002$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19299650$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hardy, Gareth A.D.</creatorcontrib><creatorcontrib>Sieg, Scott F.</creatorcontrib><creatorcontrib>Rodriguez, Benigno</creatorcontrib><creatorcontrib>Jiang, Wei</creatorcontrib><creatorcontrib>Asaad, Robert</creatorcontrib><creatorcontrib>Lederman, Michael M.</creatorcontrib><creatorcontrib>Harding, Clifford V.</creatorcontrib><title>Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression</title><title>Blood</title><addtitle>Blood</addtitle><description>Type I interferon (IFNα/β) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNα/β plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNα/β in HIV-1 infection is poorly understood. We report significant defects in IFNα/β receptor (IFNα/βR) expression, IFNα signaling, and IFNα-induced gene expression in monocytes from HIV-1–infected subjects. IFNα/βR expression correlated directly with CD4+ T-cell count and inversely with HIV-1 RNA level and expression of CD38 by memory (CD45RO+) CD8+ T cells, a measure of pathologic immune activation in HIV-1 infection associated with disease progression. In addition, monocytes from HIV-1–infected persons showed diminished responses to IFNα, including decreased induction of phosphorylated STAT1 and the classical interferon-stimulated gene produces MxA and OAS. These IFNα responses were decreased regardless of IFNα/βR expression, suggesting that regulation of intracellular signaling may contribute to unresponsiveness to IFNα/β in HIV-1 disease. Defective monocyte responses to IFNα/β may play an important role in the pathogenesis of HIV-1 infection, and decreased IFNα/βR expression may serve as a novel marker of disease progression.</description><subject>Adult</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Case-Control Studies</subject><subject>Cross-Sectional Studies</subject><subject>Disease Progression</subject><subject>Drug Resistance, Viral - immunology</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV-1 - immunology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunity, Active - drug effects</subject><subject>Immunobiology</subject><subject>Infectious diseases</subject><subject>Interferon Type I - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Monocytes - metabolism</subject><subject>Monocytes - pathology</subject><subject>Receptors, Interferon - metabolism</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV9vFCEUxYmxsWv1GxjDi76N5bIzzPBiYuqfbtKkL42vhIFLi87ACuw2bfrhpd1Nqy99Ai7nHg73R8g7YJ8ABn48TjHahjM2NAANSMaX8IIsoONDwxhnL8mCMSaaVvZwSF7n_IsxaJe8e0UOQXIpRccW5O4rZgzZF3-ri4-BlkjLzRrpivpQMDlMtegDPV39bKBuHJoHnYkp4aQLZnrtyxWddfqNKdPoqJ_nTUCqq3C7M9XBUusz6ox0neJlwpxr_Q05cHrK-Ha_HpGL798uTk6bs_Mfq5MvZ41pJZRGmm4cWyet6IaedwCiHwUI7SQ4MUqDY9v3VgqUhlurYXCiF1IMyLjD3iyPyOed7XozzmgNhpL0pNbJ19A3Kmqv_r8J_kpdxq3iYpCsY9Xg494gxT8bzEXNPhucJh0wbrISfR2nHGQVtjuhSTHnhO7xEWDqnpp6oKbuqdWz2lGrbe__DfjUtMdUBR_2Ap2NnlzSwfj8qOPQtbIyf_op1mluPSaVjcdg0PpUuSkb_fNJ_gL9BLnn</recordid><startdate>20090528</startdate><enddate>20090528</enddate><creator>Hardy, Gareth A.D.</creator><creator>Sieg, Scott F.</creator><creator>Rodriguez, Benigno</creator><creator>Jiang, Wei</creator><creator>Asaad, Robert</creator><creator>Lederman, Michael M.</creator><creator>Harding, Clifford V.</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090528</creationdate><title>Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression</title><author>Hardy, Gareth A.D. ; Sieg, Scott F. ; Rodriguez, Benigno ; Jiang, Wei ; Asaad, Robert ; Lederman, Michael M. ; Harding, Clifford V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-9c5bb4f9d6587251167b616af91f6b9ceb477d96e9c2dda18f676968e02fe7c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Case-Control Studies</topic><topic>Cross-Sectional Studies</topic><topic>Disease Progression</topic><topic>Drug Resistance, Viral - immunology</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV-1 - immunology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunity, Active - drug effects</topic><topic>Immunobiology</topic><topic>Infectious diseases</topic><topic>Interferon Type I - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Monocytes - metabolism</topic><topic>Monocytes - pathology</topic><topic>Receptors, Interferon - metabolism</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hardy, Gareth A.D.</creatorcontrib><creatorcontrib>Sieg, Scott F.</creatorcontrib><creatorcontrib>Rodriguez, Benigno</creatorcontrib><creatorcontrib>Jiang, Wei</creatorcontrib><creatorcontrib>Asaad, Robert</creatorcontrib><creatorcontrib>Lederman, Michael M.</creatorcontrib><creatorcontrib>Harding, Clifford V.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><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>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hardy, Gareth A.D.</au><au>Sieg, Scott F.</au><au>Rodriguez, Benigno</au><au>Jiang, Wei</au><au>Asaad, Robert</au><au>Lederman, Michael M.</au><au>Harding, Clifford V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2009-05-28</date><risdate>2009</risdate><volume>113</volume><issue>22</issue><spage>5497</spage><epage>5505</epage><pages>5497-5505</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Type I interferon (IFNα/β) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNα/β plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNα/β in HIV-1 infection is poorly understood. We report significant defects in IFNα/β receptor (IFNα/βR) expression, IFNα signaling, and IFNα-induced gene expression in monocytes from HIV-1–infected subjects. IFNα/βR expression correlated directly with CD4+ T-cell count and inversely with HIV-1 RNA level and expression of CD38 by memory (CD45RO+) CD8+ T cells, a measure of pathologic immune activation in HIV-1 infection associated with disease progression. In addition, monocytes from HIV-1–infected persons showed diminished responses to IFNα, including decreased induction of phosphorylated STAT1 and the classical interferon-stimulated gene produces MxA and OAS. These IFNα responses were decreased regardless of IFNα/βR expression, suggesting that regulation of intracellular signaling may contribute to unresponsiveness to IFNα/β in HIV-1 disease. Defective monocyte responses to IFNα/β may play an important role in the pathogenesis of HIV-1 infection, and decreased IFNα/βR expression may serve as a novel marker of disease progression.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>19299650</pmid><doi>10.1182/blood-2008-11-190231</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-4971 |
| ispartof | Blood, 2009-05, Vol.113 (22), p.5497-5505 |
| issn | 0006-4971 1528-0020 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2689050 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Antiviral Agents - therapeutic use Biological and medical sciences Biomarkers - blood Case-Control Studies Cross-Sectional Studies Disease Progression Drug Resistance, Viral - immunology Female Hematologic and hematopoietic diseases HIV Infections - blood HIV Infections - drug therapy HIV Infections - immunology HIV-1 - immunology Human viral diseases Humans Immunity, Active - drug effects Immunobiology Infectious diseases Interferon Type I - therapeutic use Male Medical sciences Middle Aged Monocytes - metabolism Monocytes - pathology Receptors, Interferon - metabolism Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T22%3A30%3A20IST&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=Desensitization%20to%20type%20I%20interferon%20in%20HIV-1%20infection%20correlates%20with%20markers%20of%20immune%20activation%20and%20disease%20progression&rft.jtitle=Blood&rft.au=Hardy,%20Gareth%20A.D.&rft.date=2009-05-28&rft.volume=113&rft.issue=22&rft.spage=5497&rft.epage=5505&rft.pages=5497-5505&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2008-11-190231&rft_dat=%3Cproquest_pubme%3E67299989%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=67299989&rft_id=info:pmid/19299650&rft_els_id=S0006497120373882&rfr_iscdi=true |