| pubmed-article:15220433 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C0012655 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C0205145 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C0030956 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C1704675 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C0537439 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C0332466 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C1442488 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C1521761 | lld:lifeskim |
| pubmed-article:15220433 | lifeskim:mentions | umls-concept:C0243077 | lld:lifeskim |
| pubmed-article:15220433 | pubmed:issue | 14 | lld:pubmed |
| pubmed-article:15220433 | pubmed:dateCreated | 2004-6-28 | lld:pubmed |
| pubmed-article:15220433 | pubmed:abstractText | The peptide fusion inhibitor (PFI) enfuvirtide is the first of a new class of entry inhibitors to receive FDA approval. We previously determined the susceptibility of 55 PFI-naïve-patient isolates to enfuvirtide and a second peptide inhibitor, T-649. Seven of the 55 viral isolates were insusceptible to enfuvirtide, T-649, or both inhibitors in the absence of prior exposure. To determine the molecular basis of the insusceptible phenotypes, we PCR amplified and cloned five PFI-insusceptible and one PFI-susceptible, full-length, biologically functional env genes and characterized viruses pseudotyped with the Env proteins in a single-round drug sensitivity assay. Overall, the mean 50% inhibitory concentrations of enfuvirtide and T-649 for the PFI-insusceptible Env pseudotypes were 1.4 to 1.7 log(10) and 1.2 to 1.8 log(10) greater, respectively, than those for a PFI-susceptible lab strain, NLHX; however, all of the PFI-insusceptible Env proteins conserved the sequence of a critical enfuvirtide interaction site (residues 36 to 38 of gp41, GIV) in HR-1. In contrast, multiple amino acid changes were observed C-terminal to HR-1, many of which were located in regions of HR-2 corresponding to the PFI. Nevertheless, peptides based on patient-derived HR-2 sequences were not more potent inhibitors than enfuvirtide or T-649, arguing that the basis of PFI susceptibility is not a higher-affinity, competitive HR-1/HR-2 interaction. These results demonstrate that regions of Env outside the enfuvirtide interaction site can significantly impact the PFI susceptibility of patient-derived Env, even prior to drug exposure. We hypothesize that both gp120 gene- and gp41 gene-encoded determinants that minimize the window of opportunity for PFI to bind provide a growth advantage and possibly a predisposition to resistance to this new class of drugs in vivo. | lld:pubmed |
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| pubmed-article:15220433 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15220433 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15220433 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15220433 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15220433 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:15220433 | pubmed:issn | 0022-538X | lld:pubmed |
| pubmed-article:15220433 | pubmed:author | pubmed-author:DerdeynCynthi... | lld:pubmed |
| pubmed-article:15220433 | pubmed:author | pubmed-author:HunterEricE | lld:pubmed |
| pubmed-article:15220433 | pubmed:author | pubmed-author:ShawGeorge... | lld:pubmed |
| pubmed-article:15220433 | pubmed:author | pubmed-author:DeckerJulie... | lld:pubmed |
| pubmed-article:15220433 | pubmed:author | pubmed-author:SfakianosJeff... | lld:pubmed |
| pubmed-article:15220433 | pubmed:author | pubmed-author:HeilMarintha... | lld:pubmed |
| pubmed-article:15220433 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15220433 | pubmed:volume | 78 | lld:pubmed |
| pubmed-article:15220433 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15220433 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15220433 | pubmed:pagination | 7582-9 | lld:pubmed |
| pubmed-article:15220433 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:15220433 | pubmed:meshHeading | pubmed-meshheading:15220433... | lld:pubmed |
| pubmed-article:15220433 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15220433 | pubmed:articleTitle | Determinants of human immunodeficiency virus type 1 baseline susceptibility to the fusion inhibitors enfuvirtide and T-649 reside outside the peptide interaction site. | lld:pubmed |
| pubmed-article:15220433 | pubmed:affiliation | Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA. | lld:pubmed |
| pubmed-article:15220433 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15220433 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:15220433 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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