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CXCR4 tropic human immunodeficiency virus type 1 induces an apoptotic cascade in immature infected thymocytes that resembles thymocyte negative selection
HIV-1 often replicates in the thymus of infected individuals, causing thymocyte depletion and thymic dysfunction. Nevertheless, the mechanisms by which thymocyte depletion occurs are not clear. Here we report that HIV-1 infection induced apoptosis primarily in productively infected thymocytes; aldri...
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| Published in: | Virology (New York, N.Y.) N.Y.), 2006-09, Vol.352 (2), p.268-284 |
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| Main Authors: | , , , , , |
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| cited_by | cdi_FETCH-LOGICAL-c433t-e8f5a2fc292662c3f568685943bea65969ec357350e9584c8752eafa71fc5ba83 |
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| cites | cdi_FETCH-LOGICAL-c433t-e8f5a2fc292662c3f568685943bea65969ec357350e9584c8752eafa71fc5ba83 |
| container_end_page | 284 |
| container_issue | 2 |
| container_start_page | 268 |
| container_title | Virology (New York, N.Y.) |
| container_volume | 352 |
| creator | Choudhary, Shailesh K. Walker, Russell M. Powell, Douglas M. Planelles, Vicente Walsh, Craig Camerini, David |
| description | HIV-1 often replicates in the thymus of infected individuals, causing thymocyte depletion and thymic dysfunction. Nevertheless, the mechanisms by which thymocyte depletion occurs are not clear. Here we report that HIV-1 infection induced apoptosis primarily in productively infected thymocytes; aldrithiol-2 or Efavirenz treatment largely abrogated HIV-1-induced apoptosis. Moreover, X4-HIV-1 induced apoptosis primarily in immature CD4
+ CD8
+ (DP) thymocytes whereas most mature CD4 or CD8 single-positive (SP) thymocytes were resistant to X4 HIV-1-induced apoptosis despite infection. Consistent with this, we observed significant induction of several genes involved in negative selection of DP thymocytes. Furthermore, treatment of thymocytes with cycloheximide abrogated HIV-1-induced apoptosis, implying a requirement for de novo protein synthesis. Our results suggest that HIV-1-induced apoptosis of thymocytes requires the activation of caspases and the participation of mitochondrial apoptosis effectors, which serve to amplify the apoptotic signal, a process similar to that elaborated during thymocyte negative selection. |
| doi_str_mv | 10.1016/j.virol.2006.04.037 |
| format | article |
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+ CD8
+ (DP) thymocytes whereas most mature CD4 or CD8 single-positive (SP) thymocytes were resistant to X4 HIV-1-induced apoptosis despite infection. Consistent with this, we observed significant induction of several genes involved in negative selection of DP thymocytes. Furthermore, treatment of thymocytes with cycloheximide abrogated HIV-1-induced apoptosis, implying a requirement for de novo protein synthesis. Our results suggest that HIV-1-induced apoptosis of thymocytes requires the activation of caspases and the participation of mitochondrial apoptosis effectors, which serve to amplify the apoptotic signal, a process similar to that elaborated during thymocyte negative selection.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1016/j.virol.2006.04.037</identifier><identifier>PMID: 16777169</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Apoptosis ; Apoptosis - genetics ; Apoptosis - immunology ; Apoptosis - physiology ; Caspases - metabolism ; CD4 Antigens - metabolism ; CD8 Antigens - metabolism ; Cell Differentiation ; Cyclosporine - pharmacology ; Flavonoids - pharmacology ; Gene Expression ; HIV Infections - genetics ; HIV Infections - immunology ; HIV Infections - pathology ; HIV Infections - virology ; HIV-1 ; HIV-1 - pathogenicity ; HIV-1 - physiology ; Human immunodeficiency virus 1 ; Humans ; In Vitro Techniques ; Negative selection ; Protein Biosynthesis ; Receptors, CXCR4 - physiology ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; T-Lymphocytes - pathology ; T-Lymphocytes - virology ; Thymocyte ; Virus Replication</subject><ispartof>Virology (New York, N.Y.), 2006-09, Vol.352 (2), p.268-284</ispartof><rights>2006 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-e8f5a2fc292662c3f568685943bea65969ec357350e9584c8752eafa71fc5ba83</citedby><cites>FETCH-LOGICAL-c433t-e8f5a2fc292662c3f568685943bea65969ec357350e9584c8752eafa71fc5ba83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16777169$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choudhary, Shailesh K.</creatorcontrib><creatorcontrib>Walker, Russell M.</creatorcontrib><creatorcontrib>Powell, Douglas M.</creatorcontrib><creatorcontrib>Planelles, Vicente</creatorcontrib><creatorcontrib>Walsh, Craig</creatorcontrib><creatorcontrib>Camerini, David</creatorcontrib><title>CXCR4 tropic human immunodeficiency virus type 1 induces an apoptotic cascade in immature infected thymocytes that resembles thymocyte negative selection</title><title>Virology (New York, N.Y.)</title><addtitle>Virology</addtitle><description>HIV-1 often replicates in the thymus of infected individuals, causing thymocyte depletion and thymic dysfunction. Nevertheless, the mechanisms by which thymocyte depletion occurs are not clear. Here we report that HIV-1 infection induced apoptosis primarily in productively infected thymocytes; aldrithiol-2 or Efavirenz treatment largely abrogated HIV-1-induced apoptosis. Moreover, X4-HIV-1 induced apoptosis primarily in immature CD4
+ CD8
+ (DP) thymocytes whereas most mature CD4 or CD8 single-positive (SP) thymocytes were resistant to X4 HIV-1-induced apoptosis despite infection. Consistent with this, we observed significant induction of several genes involved in negative selection of DP thymocytes. Furthermore, treatment of thymocytes with cycloheximide abrogated HIV-1-induced apoptosis, implying a requirement for de novo protein synthesis. Our results suggest that HIV-1-induced apoptosis of thymocytes requires the activation of caspases and the participation of mitochondrial apoptosis effectors, which serve to amplify the apoptotic signal, a process similar to that elaborated during thymocyte negative selection.</description><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis - immunology</subject><subject>Apoptosis - physiology</subject><subject>Caspases - metabolism</subject><subject>CD4 Antigens - metabolism</subject><subject>CD8 Antigens - metabolism</subject><subject>Cell Differentiation</subject><subject>Cyclosporine - pharmacology</subject><subject>Flavonoids - pharmacology</subject><subject>Gene Expression</subject><subject>HIV Infections - genetics</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - pathology</subject><subject>HIV Infections - virology</subject><subject>HIV-1</subject><subject>HIV-1 - pathogenicity</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Negative selection</subject><subject>Protein Biosynthesis</subject><subject>Receptors, CXCR4 - physiology</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - pathology</subject><subject>T-Lymphocytes - virology</subject><subject>Thymocyte</subject><subject>Virus Replication</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFkcuqFDEQhoMonvHoEwiSlbsec0964UIGb3BAEAV3IZOudjJ0d9okPdCP4tuauYA7XSVFfV8V1I_QS0q2lFD15rg9hRSHLSNEbYnYEq4foQ0lrWoIF_Qx2hAiWKMMY3foWc5HUmutyVN0R5XWmqp2g37vfuy-ClxSnIPHh2V0Ew7juEyxgz74AJNfcd2zZFzWGTDFYeoWDxlX0M1xLrFU0bvsXQe1ebZdWdL534Mv0OFyWMfo11KlcnAFJ8gw7odLeevgCX66Ek6AMwzVCnF6jp70bsjw4vbeo-8f3n_bfWoevnz8vHv30HjBeWnA9NKx3rOWKcU876UyyshW8D04JVvVgudSc0mglUZ4oyUD1ztNey_3zvB79Po6d07x1wK52DFkD8PgJohLtspoJQyR_wVpywVnhlWQX0GfYs4JejunMLq0WkrsOTp7tJfo7Dk6S4St0VXr1W38sh-h--vcsqrA2ysA9RqnAMnmSz7QhVRPZrsY_rngDxfgryY</recordid><startdate>20060901</startdate><enddate>20060901</enddate><creator>Choudhary, Shailesh K.</creator><creator>Walker, Russell M.</creator><creator>Powell, Douglas M.</creator><creator>Planelles, Vicente</creator><creator>Walsh, Craig</creator><creator>Camerini, David</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20060901</creationdate><title>CXCR4 tropic human immunodeficiency virus type 1 induces an apoptotic cascade in immature infected thymocytes that resembles thymocyte negative selection</title><author>Choudhary, Shailesh K. ; 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Nevertheless, the mechanisms by which thymocyte depletion occurs are not clear. Here we report that HIV-1 infection induced apoptosis primarily in productively infected thymocytes; aldrithiol-2 or Efavirenz treatment largely abrogated HIV-1-induced apoptosis. Moreover, X4-HIV-1 induced apoptosis primarily in immature CD4
+ CD8
+ (DP) thymocytes whereas most mature CD4 or CD8 single-positive (SP) thymocytes were resistant to X4 HIV-1-induced apoptosis despite infection. Consistent with this, we observed significant induction of several genes involved in negative selection of DP thymocytes. Furthermore, treatment of thymocytes with cycloheximide abrogated HIV-1-induced apoptosis, implying a requirement for de novo protein synthesis. Our results suggest that HIV-1-induced apoptosis of thymocytes requires the activation of caspases and the participation of mitochondrial apoptosis effectors, which serve to amplify the apoptotic signal, a process similar to that elaborated during thymocyte negative selection.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16777169</pmid><doi>10.1016/j.virol.2006.04.037</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Virology (New York, N.Y.), 2006-09, Vol.352 (2), p.268-284 |
| issn | 0042-6822 1096-0341 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68764805 |
| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS; ScienceDirect Journals |
| subjects | Apoptosis Apoptosis - genetics Apoptosis - immunology Apoptosis - physiology Caspases - metabolism CD4 Antigens - metabolism CD8 Antigens - metabolism Cell Differentiation Cyclosporine - pharmacology Flavonoids - pharmacology Gene Expression HIV Infections - genetics HIV Infections - immunology HIV Infections - pathology HIV Infections - virology HIV-1 HIV-1 - pathogenicity HIV-1 - physiology Human immunodeficiency virus 1 Humans In Vitro Techniques Negative selection Protein Biosynthesis Receptors, CXCR4 - physiology T-Lymphocytes - drug effects T-Lymphocytes - immunology T-Lymphocytes - pathology T-Lymphocytes - virology Thymocyte Virus Replication |
| title | CXCR4 tropic human immunodeficiency virus type 1 induces an apoptotic cascade in immature infected thymocytes that resembles thymocyte negative selection |
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