Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1
Intrarectal infection between men who have sex with men represents a predominant form of human immunodeficiency virus (HIV) transmission in developed countries. Currently there are no adequate small animal models that recapitulate intrarectal HIV transmission. Here we demonstrate that human lymphocy...
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Veröffentlicht in: | The Journal of experimental medicine 2007-04, Vol.204 (4), p.705-714 |
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creator | Sun, Zhifeng Denton, Paul W Estes, Jacob D Othieno, Florence A Wei, Bangdong L Wege, Anja K Melkus, Michael W Padgett-Thomas, Angela Zupancic, Mary Haase, Ashley T Garcia, J Victor |
description | Intrarectal infection between men who have sex with men represents a predominant form of human immunodeficiency virus (HIV) transmission in developed countries. Currently there are no adequate small animal models that recapitulate intrarectal HIV transmission. Here we demonstrate that human lymphocytes generated in situ from hematopoietic stem cells reconstitute the gastrointestinal tract of humanized mice with human CD4(+) T cells rendering them susceptible to intrarectal HIV transmission. HIV infection after a single intrarectal inoculation results in systemic infection with depletion of CD4(+) T cells in gut-associated lymphoid tissue and other pathologic sequela that closely mimics those observed in HIV infected humans. This novel model provides the basis for the development and evaluation of novel approaches aimed at immune reconstitution of human gut-associated lymphoid tissue and for the development, testing, and implementation of microbicides to prevent intrarectal HIV-1 transmission. |
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Currently there are no adequate small animal models that recapitulate intrarectal HIV transmission. Here we demonstrate that human lymphocytes generated in situ from hematopoietic stem cells reconstitute the gastrointestinal tract of humanized mice with human CD4(+) T cells rendering them susceptible to intrarectal HIV transmission. HIV infection after a single intrarectal inoculation results in systemic infection with depletion of CD4(+) T cells in gut-associated lymphoid tissue and other pathologic sequela that closely mimics those observed in HIV infected humans. This novel model provides the basis for the development and evaluation of novel approaches aimed at immune reconstitution of human gut-associated lymphoid tissue and for the development, testing, and implementation of microbicides to prevent intrarectal HIV-1 transmission.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20062411</identifier><identifier>PMID: 17389241</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Animals ; Bone Marrow - immunology ; Bone Marrow - metabolism ; Brief Definitive Reports ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - pathology ; Cell Proliferation ; HIV Infections - immunology ; HIV Infections - pathology ; HIV Infections - transmission ; HIV Infections - virology ; HIV-1 - pathogenicity ; HIV-1 - physiology ; Humans ; Liver - immunology ; Liver - metabolism ; Lymphoid Tissue - immunology ; Lymphoid Tissue - metabolism ; Mice ; Phenotype ; Receptors, CCR5 - metabolism ; Receptors, CXCR4 - metabolism ; Rectum - immunology ; Rectum - injuries ; Rectum - pathology ; Rectum - virology ; Thymus Gland - immunology ; Thymus Gland - metabolism</subject><ispartof>The Journal of experimental medicine, 2007-04, Vol.204 (4), p.705-714</ispartof><rights>Copyright © 2007, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-5a6d5ca57562b8b7d6aa7261c9c8985e2c3169b28fa59eab4eb0a38880f8d8393</citedby><cites>FETCH-LOGICAL-c382t-5a6d5ca57562b8b7d6aa7261c9c8985e2c3169b28fa59eab4eb0a38880f8d8393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17389241$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Zhifeng</creatorcontrib><creatorcontrib>Denton, Paul W</creatorcontrib><creatorcontrib>Estes, Jacob D</creatorcontrib><creatorcontrib>Othieno, Florence A</creatorcontrib><creatorcontrib>Wei, Bangdong L</creatorcontrib><creatorcontrib>Wege, Anja K</creatorcontrib><creatorcontrib>Melkus, Michael W</creatorcontrib><creatorcontrib>Padgett-Thomas, Angela</creatorcontrib><creatorcontrib>Zupancic, Mary</creatorcontrib><creatorcontrib>Haase, Ashley T</creatorcontrib><creatorcontrib>Garcia, J Victor</creatorcontrib><title>Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Intrarectal infection between men who have sex with men represents a predominant form of human immunodeficiency virus (HIV) transmission in developed countries. Currently there are no adequate small animal models that recapitulate intrarectal HIV transmission. Here we demonstrate that human lymphocytes generated in situ from hematopoietic stem cells reconstitute the gastrointestinal tract of humanized mice with human CD4(+) T cells rendering them susceptible to intrarectal HIV transmission. HIV infection after a single intrarectal inoculation results in systemic infection with depletion of CD4(+) T cells in gut-associated lymphoid tissue and other pathologic sequela that closely mimics those observed in HIV infected humans. This novel model provides the basis for the development and evaluation of novel approaches aimed at immune reconstitution of human gut-associated lymphoid tissue and for the development, testing, and implementation of microbicides to prevent intrarectal HIV-1 transmission.</description><subject>Animals</subject><subject>Bone Marrow - immunology</subject><subject>Bone Marrow - metabolism</subject><subject>Brief Definitive Reports</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - pathology</subject><subject>Cell Proliferation</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - pathology</subject><subject>HIV Infections - transmission</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - pathogenicity</subject><subject>HIV-1 - physiology</subject><subject>Humans</subject><subject>Liver - immunology</subject><subject>Liver - metabolism</subject><subject>Lymphoid Tissue - immunology</subject><subject>Lymphoid Tissue - metabolism</subject><subject>Mice</subject><subject>Phenotype</subject><subject>Receptors, CCR5 - metabolism</subject><subject>Receptors, CXCR4 - metabolism</subject><subject>Rectum - immunology</subject><subject>Rectum - injuries</subject><subject>Rectum - pathology</subject><subject>Rectum - virology</subject><subject>Thymus Gland - immunology</subject><subject>Thymus Gland - metabolism</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUclOwzAQtRCIlsKNM_KJC03xEifOBQmVpZWQuBSuluNMqKssJU5A5etxaNlOHvst45mH0CklE0pkeLmCcsIIiVhI6R4aUhGSIBFc7qMhIYwFlJB4gI6cWxFCw1BEh2hAYy4TLxiicl61jW7AtLrAvqpcaZ2zdTXGbuNaKK3Btso9_vWmqwxPb8ILvMAGigJnsC6ghzwJL7tSV_YDMuxVsJP527ttl3g2fw7oMTrIdeHgZHeO0NPd7WI6Cx4e7-fT64fAcMnaQOgoE0aLWEQslWmcRVrHLKImMTKRApjhNEpSJnMtEtBpCCnRXEpJcplJnvARutr6rru0hMxAP2Sh1o0tdbNRtbbqP1LZpXqp3xSjVArBvcH5zqCpXztwrfJr6SfWFdSdUzHhiRCh8MTxlmia2rkG8p8mlKg-H-XzUd_5ePrZ34_9kneB8E96bYzl</recordid><startdate>20070416</startdate><enddate>20070416</enddate><creator>Sun, Zhifeng</creator><creator>Denton, Paul W</creator><creator>Estes, Jacob D</creator><creator>Othieno, Florence A</creator><creator>Wei, Bangdong L</creator><creator>Wege, Anja K</creator><creator>Melkus, Michael W</creator><creator>Padgett-Thomas, Angela</creator><creator>Zupancic, Mary</creator><creator>Haase, Ashley T</creator><creator>Garcia, J Victor</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>20070416</creationdate><title>Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1</title><author>Sun, Zhifeng ; Denton, Paul W ; Estes, Jacob D ; Othieno, Florence A ; Wei, Bangdong L ; Wege, Anja K ; Melkus, Michael W ; Padgett-Thomas, Angela ; Zupancic, Mary ; Haase, Ashley T ; Garcia, J Victor</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-5a6d5ca57562b8b7d6aa7261c9c8985e2c3169b28fa59eab4eb0a38880f8d8393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Bone Marrow - immunology</topic><topic>Bone Marrow - metabolism</topic><topic>Brief Definitive Reports</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD4-Positive T-Lymphocytes - pathology</topic><topic>Cell Proliferation</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - pathology</topic><topic>HIV Infections - transmission</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - pathogenicity</topic><topic>HIV-1 - physiology</topic><topic>Humans</topic><topic>Liver - immunology</topic><topic>Liver - metabolism</topic><topic>Lymphoid Tissue - immunology</topic><topic>Lymphoid Tissue - metabolism</topic><topic>Mice</topic><topic>Phenotype</topic><topic>Receptors, CCR5 - metabolism</topic><topic>Receptors, CXCR4 - metabolism</topic><topic>Rectum - immunology</topic><topic>Rectum - injuries</topic><topic>Rectum - pathology</topic><topic>Rectum - virology</topic><topic>Thymus Gland - immunology</topic><topic>Thymus Gland - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Zhifeng</creatorcontrib><creatorcontrib>Denton, Paul W</creatorcontrib><creatorcontrib>Estes, Jacob D</creatorcontrib><creatorcontrib>Othieno, Florence A</creatorcontrib><creatorcontrib>Wei, Bangdong L</creatorcontrib><creatorcontrib>Wege, Anja K</creatorcontrib><creatorcontrib>Melkus, Michael W</creatorcontrib><creatorcontrib>Padgett-Thomas, Angela</creatorcontrib><creatorcontrib>Zupancic, Mary</creatorcontrib><creatorcontrib>Haase, Ashley T</creatorcontrib><creatorcontrib>Garcia, J Victor</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>Sun, Zhifeng</au><au>Denton, Paul W</au><au>Estes, Jacob D</au><au>Othieno, Florence A</au><au>Wei, Bangdong L</au><au>Wege, Anja K</au><au>Melkus, Michael W</au><au>Padgett-Thomas, Angela</au><au>Zupancic, Mary</au><au>Haase, Ashley T</au><au>Garcia, J Victor</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2007-04-16</date><risdate>2007</risdate><volume>204</volume><issue>4</issue><spage>705</spage><epage>714</epage><pages>705-714</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Intrarectal infection between men who have sex with men represents a predominant form of human immunodeficiency virus (HIV) transmission in developed countries. Currently there are no adequate small animal models that recapitulate intrarectal HIV transmission. Here we demonstrate that human lymphocytes generated in situ from hematopoietic stem cells reconstitute the gastrointestinal tract of humanized mice with human CD4(+) T cells rendering them susceptible to intrarectal HIV transmission. HIV infection after a single intrarectal inoculation results in systemic infection with depletion of CD4(+) T cells in gut-associated lymphoid tissue and other pathologic sequela that closely mimics those observed in HIV infected humans. This novel model provides the basis for the development and evaluation of novel approaches aimed at immune reconstitution of human gut-associated lymphoid tissue and for the development, testing, and implementation of microbicides to prevent intrarectal HIV-1 transmission.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>17389241</pmid><doi>10.1084/jem.20062411</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Bone Marrow - immunology Bone Marrow - metabolism Brief Definitive Reports CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - pathology Cell Proliferation HIV Infections - immunology HIV Infections - pathology HIV Infections - transmission HIV Infections - virology HIV-1 - pathogenicity HIV-1 - physiology Humans Liver - immunology Liver - metabolism Lymphoid Tissue - immunology Lymphoid Tissue - metabolism Mice Phenotype Receptors, CCR5 - metabolism Receptors, CXCR4 - metabolism Rectum - immunology Rectum - injuries Rectum - pathology Rectum - virology Thymus Gland - immunology Thymus Gland - metabolism |
title | Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1 |
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