Linked Life Data

21338625

Source:http://linkedlifedata.com/resource/pubmed/id/21338625

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-4-12
pubmed:abstractText
To better understand the mechanism of HIV group-specific antigen (Gag) and protease (PR) co-evolution in drug-resistance acquisition, we analyzed a drug-resistance case by both bioinformatics and virological methods. We especially considered the quality of sequence data and analytical accuracy by introducing single-genome sequencing (SGS) and Spidermonkey/Bayesian graphical models (BGM) analysis, respectively. We analyzed 129 HIV-1 Gag-PR linkage sequences obtained from 8 time points, and the resulting sequences were applied to the Spidermonkey co-evolution analysis program, which identified ten mutation pairs as significantly co-evolving. Among these, we focused on associations between Gag-P453L, the P5' position of the p1/p6 cleavage-site mutation, and PR-D30N/N88D nelfinavir-resistant mutations, and attempted to clarify their virological significance in vitro by constructing recombinant clones. The results showed that P453L(Gag) has the potential to improve replication capacity and the Gag processing efficiency of viruses with D30N(PR)/N88D(PR) but has little effect on nelfinavir susceptibility. Homology modeling analysis suggested that hydrogen bonds between the 30th PR residue and the R452Gag are disturbed by the D30N(PR) mutation, but the impaired interaction is compensated by P453L(Gag) generating new hydrophobic interactions. Furthermore, database analysis indicated that the P453L(Gag)/D30N(PR)/N88D(PR) association was not specific only to our clinical case, but was common among AIDS patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1872-9096
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-41
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Within-host co-evolution of Gag P453L and protease D30N/N88D demonstrates virological advantage in a highly protease inhibitor-exposed HIV-1 case.
pubmed:affiliation
School of Biomedical Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't