Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1997-11-13
pubmed:abstractText
A triterpene derived from betulinic acid (RPR103611) blocks human immunodeficiency virus type 1 (HIV-1) infection and fusion of CD4+ cells with cells expressing HIV-1 envelope proteins (gp120 and gp41), suggesting an effect on virus entry. This compound did not block infection by a subtype D HIV-1 strain (NDK) or cell-cell fusion mediated by the NDK envelope proteins. The genetic basis of drug resistance was therefore addressed by testing envelope chimeras derived from NDK and a drug-sensitive HIV-1 strain (LAI, subtype B). A drug-resistant phenotype was observed for all chimeras bearing the ectodomain of NDK gp41, while the origins of gp120 and of the membrane anchor and cytoplasmic domains of gp41 had no apparent role. The envelope gene of a LAI variant, fully resistant to the antiviral effect of RPR103611, was cloned and sequenced. Its product differed from the parental sequence at two positions in gp41, with changes of arginine 22 to alanine (R22A) and isoleucine 84 to serine (I84S), the gp120 being identical. In the context of LAI gp41, the I84S substitution was sufficient for drug resistance. Therefore, in two different systems, differences in gp41 were associated with sensitivity or resistance to RPR103611. Modifications of gp41 can affect the quaternary structure of gp120 and gp41 and the accessibility of gp120 to antiviral agents such as neutralizing antibodies. However, a direct effect of RPR103611 on a gp41 target must also be envisioned, in agreement with the blocking of apparently late steps of HIV-1 entry. This compound could be a valuable tool for structure-function studies of gp41.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-1347667, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-1438243, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-1551875, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-1683726, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-1742075, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-2364015, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-2566170, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-2788443, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-2806917, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-2838179, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-7483259, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-7530400, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-7576913, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-7903129, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-7906414, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-7937889, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-7983757, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8009858, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8072525, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8107256, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8162421, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8170948, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8289347, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8474172, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8500173, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8551604, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8627756, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8794008, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8846219, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8892962, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8906795, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8906796, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8946819, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-8970955, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-9060691, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-9108481, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-9163431, http://linkedlifedata.com/resource/pubmed/commentcorrection/9343174-9287172
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-538X
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8230-6
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Resistance to a drug blocking human immunodeficiency virus type 1 entry (RPR103611) is conferred by mutations in gp41.
pubmed:affiliation
INSERM, Institut Cochin de Génétique Moléculaire, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't