Constitutively Dead, Conditionally Live HIV-1 Genomes
An effective vaccine against AIDS is unlikely to be available for many years. As we approach two decades since the first identification of human immunodeficiency virus, type 1 (HIV-1), currently, only one subunit vaccine candidate has reached phase 3 of clinical trials. The subunit approach has been...
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| Veröffentlicht in: | The Journal of biological chemistry 2001-08, Vol.276 (34), p.32184-32190 |
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| container_issue | 34 |
| container_start_page | 32184 |
| container_title | The Journal of biological chemistry |
| container_volume | 276 |
| creator | Smith, Stephen M. Khoroshev, Mikhail Marx, Preston A. Orenstein, Jan Jeang, Kuan-Teh |
| description | An effective vaccine against AIDS is unlikely to be available for many years. As we approach two decades since the first identification
of human immunodeficiency virus, type 1 (HIV-1), currently, only one subunit vaccine candidate has reached phase 3 of clinical
trials. The subunit approach has been criticized for its inability to elicit effectively cytotoxic T-lymphocyte (CTL) response,
which is felt by many to be needed for protection against HIV-1 infection. In subhuman primates, a live attenuated simian
immunodeficiency virus (SIV) vaccine candidate, capable of inducing CTL, has been found to confer prophylactic immunity sufficient
to prevent simian AIDS. Because replication competent (live) attenuated viruses could over time revert to virulence, such
a live attenuated approach has largely been dismissed for HIV-1. Here, we describe the creation of constitutively dead conditionally
live (CDCL) HIV-1 genomes. These genomes are constitutively defective for the Tat/TAR axis and are conditionally dependent
on tetracycline for attenuated replication with robust expression of viral antigens. Our results suggest that CDCL genomes
merit consideration as safer âliveâ attenuated HIV-1 vaccine candidates. |
| doi_str_mv | 10.1074/jbc.M101604200 |
| format | Article |
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of human immunodeficiency virus, type 1 (HIV-1), currently, only one subunit vaccine candidate has reached phase 3 of clinical
trials. The subunit approach has been criticized for its inability to elicit effectively cytotoxic T-lymphocyte (CTL) response,
which is felt by many to be needed for protection against HIV-1 infection. In subhuman primates, a live attenuated simian
immunodeficiency virus (SIV) vaccine candidate, capable of inducing CTL, has been found to confer prophylactic immunity sufficient
to prevent simian AIDS. Because replication competent (live) attenuated viruses could over time revert to virulence, such
a live attenuated approach has largely been dismissed for HIV-1. Here, we describe the creation of constitutively dead conditionally
live (CDCL) HIV-1 genomes. These genomes are constitutively defective for the Tat/TAR axis and are conditionally dependent
on tetracycline for attenuated replication with robust expression of viral antigens. Our results suggest that CDCL genomes
merit consideration as safer âliveâ attenuated HIV-1 vaccine candidates.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M101604200</identifier><identifier>PMID: 11397795</identifier><language>eng</language><publisher>American Society for Biochemistry and Molecular Biology</publisher><ispartof>The Journal of biological chemistry, 2001-08, Vol.276 (34), p.32184-32190</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1530-f6e1c58d5d1f9f45015129751f1ceb8731e882a8e0f2d2b866f35d954274673b3</citedby><cites>FETCH-LOGICAL-c1530-f6e1c58d5d1f9f45015129751f1ceb8731e882a8e0f2d2b866f35d954274673b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Smith, Stephen M.</creatorcontrib><creatorcontrib>Khoroshev, Mikhail</creatorcontrib><creatorcontrib>Marx, Preston A.</creatorcontrib><creatorcontrib>Orenstein, Jan</creatorcontrib><creatorcontrib>Jeang, Kuan-Teh</creatorcontrib><title>Constitutively Dead, Conditionally Live HIV-1 Genomes</title><title>The Journal of biological chemistry</title><description>An effective vaccine against AIDS is unlikely to be available for many years. As we approach two decades since the first identification
of human immunodeficiency virus, type 1 (HIV-1), currently, only one subunit vaccine candidate has reached phase 3 of clinical
trials. The subunit approach has been criticized for its inability to elicit effectively cytotoxic T-lymphocyte (CTL) response,
which is felt by many to be needed for protection against HIV-1 infection. In subhuman primates, a live attenuated simian
immunodeficiency virus (SIV) vaccine candidate, capable of inducing CTL, has been found to confer prophylactic immunity sufficient
to prevent simian AIDS. Because replication competent (live) attenuated viruses could over time revert to virulence, such
a live attenuated approach has largely been dismissed for HIV-1. Here, we describe the creation of constitutively dead conditionally
live (CDCL) HIV-1 genomes. These genomes are constitutively defective for the Tat/TAR axis and are conditionally dependent
on tetracycline for attenuated replication with robust expression of viral antigens. Our results suggest that CDCL genomes
merit consideration as safer âliveâ attenuated HIV-1 vaccine candidates.</description><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNpFj8tLxDAYxIMo7rp69dyDR1u_L48mOUrV3YWKFxVvoY_EZulDmqrsf29lBecyMMMM_Ai5REgQJL_ZlVXyiIApcApwRJYIisVM4NsxWQJQjDUVakHOQtjBLK7xlCwQmZZSiyUR2dCHyU-fk_-y7T66s0V9Hc1h7Sc_9EU7Z_lcRZvta4zR2vZDZ8M5OXFFG-zFn6_Iy8P9c7aJ86f1NrvN4woFg9ilFiuhalGj044LQIFUS4EOK1sqydAqRQtlwdGalipNHRO1FpxKnkpWshVJDr_VOIQwWmc-Rt8V494gmF9-M_Obf_55cHUYNP69-fajNaUfqsZ2hsrUMG4YRcXZD9HSVdI</recordid><startdate>20010824</startdate><enddate>20010824</enddate><creator>Smith, Stephen M.</creator><creator>Khoroshev, Mikhail</creator><creator>Marx, Preston A.</creator><creator>Orenstein, Jan</creator><creator>Jeang, Kuan-Teh</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20010824</creationdate><title>Constitutively Dead, Conditionally Live HIV-1 Genomes</title><author>Smith, Stephen M. ; Khoroshev, Mikhail ; Marx, Preston A. ; Orenstein, Jan ; Jeang, Kuan-Teh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1530-f6e1c58d5d1f9f45015129751f1ceb8731e882a8e0f2d2b866f35d954274673b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smith, Stephen M.</creatorcontrib><creatorcontrib>Khoroshev, Mikhail</creatorcontrib><creatorcontrib>Marx, Preston A.</creatorcontrib><creatorcontrib>Orenstein, Jan</creatorcontrib><creatorcontrib>Jeang, Kuan-Teh</creatorcontrib><collection>CrossRef</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smith, Stephen M.</au><au>Khoroshev, Mikhail</au><au>Marx, Preston A.</au><au>Orenstein, Jan</au><au>Jeang, Kuan-Teh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Constitutively Dead, Conditionally Live HIV-1 Genomes</atitle><jtitle>The Journal of biological chemistry</jtitle><date>2001-08-24</date><risdate>2001</risdate><volume>276</volume><issue>34</issue><spage>32184</spage><epage>32190</epage><pages>32184-32190</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>An effective vaccine against AIDS is unlikely to be available for many years. As we approach two decades since the first identification
of human immunodeficiency virus, type 1 (HIV-1), currently, only one subunit vaccine candidate has reached phase 3 of clinical
trials. The subunit approach has been criticized for its inability to elicit effectively cytotoxic T-lymphocyte (CTL) response,
which is felt by many to be needed for protection against HIV-1 infection. In subhuman primates, a live attenuated simian
immunodeficiency virus (SIV) vaccine candidate, capable of inducing CTL, has been found to confer prophylactic immunity sufficient
to prevent simian AIDS. Because replication competent (live) attenuated viruses could over time revert to virulence, such
a live attenuated approach has largely been dismissed for HIV-1. Here, we describe the creation of constitutively dead conditionally
live (CDCL) HIV-1 genomes. These genomes are constitutively defective for the Tat/TAR axis and are conditionally dependent
on tetracycline for attenuated replication with robust expression of viral antigens. Our results suggest that CDCL genomes
merit consideration as safer âliveâ attenuated HIV-1 vaccine candidates.</abstract><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>11397795</pmid><doi>10.1074/jbc.M101604200</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0021-9258 1083-351X |
| language | eng |
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| source | EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| title | Constitutively Dead, Conditionally Live HIV-1 Genomes |
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