| pubmed-article:16956950 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16956950 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
| pubmed-article:16956950 | lifeskim:mentions | umls-concept:C1254042 | lld:lifeskim |
| pubmed-article:16956950 | lifeskim:mentions | umls-concept:C1999216 | lld:lifeskim |
| pubmed-article:16956950 | lifeskim:mentions | umls-concept:C0683598 | lld:lifeskim |
| pubmed-article:16956950 | lifeskim:mentions | umls-concept:C1533691 | lld:lifeskim |
| pubmed-article:16956950 | lifeskim:mentions | umls-concept:C1999799 | lld:lifeskim |
| pubmed-article:16956950 | lifeskim:mentions | umls-concept:C1433070 | lld:lifeskim |
| pubmed-article:16956950 | pubmed:issue | 22 | lld:pubmed |
| pubmed-article:16956950 | pubmed:dateCreated | 2006-10-30 | lld:pubmed |
| pubmed-article:16956950 | pubmed:abstractText | 3-O-(3',3'-dimethylsuccinyl)betulinic acid (PA-457 or bevirimat) potently inhibits human immunodeficiency virus type 1 (HIV-1) maturation by blocking a late step in the Gag processing pathway, specifically the cleavage of SP1 from the C terminus of capsid (CA). To gain insights into the mechanism(s) by which HIV-1 could evolve resistance to PA-457 and to evaluate the likelihood of such resistance arising in PA-457-treated patients, we sought to identify and characterize a broad spectrum of HIV-1 variants capable of conferring resistance to this compound. Numerous independent rounds of selection repeatedly identified six single-amino-acid substitutions that independently confer PA-457 resistance: three at or near the C terminus of CA (CA-H226Y, -L231F, and -L231M) and three at the first and third residues of SP1 (SP1-A1V, -A3T, and -A3V). We determined that mutations CA-H226Y, CA-L231F, CA-L231M, and SP1-A1V do not impose a significant replication defect on HIV-1 in culture. In contrast, mutations SP1-A3V and -A3T severely impaired virus replication and inhibited virion core condensation. The replication defect imposed by SP1-A3V was reversed by a second-site compensatory mutation in CA (CA-G225S). Intriguingly, high concentrations of PA-457 enhanced the maturation of SP1 residue 3 mutants. The different phenotypes associated with mutations that confer PA-457 resistance suggest the existence of multiple mechanisms by which HIV-1 can evolve resistance to this maturation inhibitor. These findings have implications for the ongoing development of PA-457 to treat HIV-1 infection in vivo. | lld:pubmed |
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| pubmed-article:16956950 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16956950 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16956950 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16956950 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16956950 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:16956950 | pubmed:issn | 0022-538X | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:FreedEric OEO | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:NagashimaKuni... | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:LiFengF | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:SakalianMicha... | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:AdamsonCather... | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:Goila-GaurRit... | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:SalzwedelKarl... | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:WildCarl TCT | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:AblanSherimay... | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:BoerasIoanaI | lld:pubmed |
| pubmed-article:16956950 | pubmed:author | pubmed-author:SoheilianFerr... | lld:pubmed |
| pubmed-article:16956950 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16956950 | pubmed:volume | 80 | lld:pubmed |
| pubmed-article:16956950 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16956950 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16956950 | pubmed:pagination | 10957-71 | lld:pubmed |
| pubmed-article:16956950 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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