Source:http://linkedlifedata.com/resource/pubmed/id/11983249
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
2002-5-1
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pubmed:abstractText |
The efficacy of candidate AIDS vaccines to mediate protection against viral infection and pathogenesis is evaluated, at a preclinical stage, in animal models. One model that is favored because the infecting virus is closely related to HIV-1 and because of the rapidity of pathogenic outcomes is the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae. We investigated the basis for the depletion of CD4(+) T lymphocytes in a SHIV-macaque model. Molecularly cloned SHIVs, SHIV-89.6 and SHIV-KB9, differ in the ability to cause CD4(+) T-cell loss at a given level of virus replication in monkeys. The envelope glycoproteins of the pathogenic SHIV-KB9 mediate membrane-fusion in cultured T lymphocytes more efficiently than the envelope glycoproteins of the non-pathogenic SHIV-89.6. The minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity was sufficient to convert SHIV-89.6 into a virus that causes profound CD4(+) T-cell depletion in monkeys. Conversely, two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins also attenuated the CD4(+) T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4(+) T lymphocytes in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0264-410X
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pubmed:author |
pubmed-author:AxthelmMichael KMK,
pubmed-author:Etemad-MoghadamBijanB,
pubmed-author:FantonJohn WJW,
pubmed-author:GelmanRebeccaR,
pubmed-author:LetvinNorman LNL,
pubmed-author:ManolaJudithJ,
pubmed-author:RaczPaulP,
pubmed-author:RhoneDanielaD,
pubmed-author:SodroskiJosephJ,
pubmed-author:SteenbekeTavisT,
pubmed-author:SunYingY,
pubmed-author:Tenner-RaczKlaraK
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1934-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11983249-Amino Acid Substitution,
pubmed-meshheading:11983249-Animals,
pubmed-meshheading:11983249-CD4-Positive T-Lymphocytes,
pubmed-meshheading:11983249-Cytopathogenic Effect, Viral,
pubmed-meshheading:11983249-Genes, env,
pubmed-meshheading:11983249-HIV Envelope Protein gp120,
pubmed-meshheading:11983249-HIV-1,
pubmed-meshheading:11983249-Macaca mulatta,
pubmed-meshheading:11983249-Membrane Fusion,
pubmed-meshheading:11983249-Simian Acquired Immunodeficiency Syndrome,
pubmed-meshheading:11983249-Simian immunodeficiency virus,
pubmed-meshheading:11983249-Structure-Activity Relationship,
pubmed-meshheading:11983249-Virus Replication
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pubmed:year |
2002
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pubmed:articleTitle |
Understanding the basis of CD4(+) T-cell depletion in macaques infected by a simian-human immunodeficiency virus.
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pubmed:affiliation |
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Review
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