Mapping sites of positive selection and amino acid diversification in the HIV genome: An alternative approach to vaccine design?

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dc.contributor.authorDe Oliveira T.
dc.contributor.authorSalemi M.
dc.contributor.authorGordon M.
dc.contributor.authorVandamme A.-M.
dc.contributor.authorVan Rensburg E.J.
dc.contributor.authorEngelbrecht S.
dc.contributor.authorCoovadia H.M.
dc.contributor.authorCassol S.
dc.date.accessioned2011-05-15T16:16:29Z
dc.date.available2011-05-15T16:16:29Z
dc.date.issued2004
dc.description.abstractA safe and effective HIV-1 vaccine is urgently needed to control the worldwide AIDS epidemic. Traditional methods of vaccine development have been frustratingly slow, and it is becoming increasingly apparent that radical new approaches may be required. Computational and mathematical approaches, combined with evolutionary reasoning, may provide new insights for the design of an efficacious AIDS vaccine. Here, we used codon-based substitution models and maximum-likelihood (ML) methods to identify positively selected sites that are likely to be involved in the immune control of HIV-1. Analysis of subtypes B and C revealed widespread adaptive evolution. Positively selected amino acids were detected in all nine HIV-1 proteins, including Env. Of particular interest was the high level of positive selection within the C-terminal regions of the immediate-early regulatory proteins, Tat and Rev. Many of the amino acid replacements were associated with the emergence of novel (or alternative) myristylation and casein kinase II (CKII) phosphorylation sites. The impact of these changes on the conformation and antigenicity of Tat and Rev remains to be established. In rhesus macaques, a single CTL-associated amino substitution in Tat has been linked to escape from acute SIV infection. Understanding the relationship between host-driven positive selection and antigenic variation may lead to the development of novel vaccine strategies that preempt the escape process.
dc.description.versionArticle
dc.identifier.citationGenetics
dc.identifier.citation167
dc.identifier.citation3
dc.identifier.issn00166731
dc.identifier.other10.1534/genetics.103.018135
dc.identifier.urihttp://hdl.handle.net/10019.1/13800
dc.subjectamino acid
dc.subjectcasein kinase II
dc.subjectepitope
dc.subjectHuman immunodeficiency virus vaccine
dc.subjectimmediate early protein
dc.subjectpeptide
dc.subjectRev protein
dc.subjecttransactivator protein
dc.subjectvirus envelope protein
dc.subjectvirus protein
dc.subjectamino acid sequence
dc.subjectamino acid substitution
dc.subjectantigenicity
dc.subjectarticle
dc.subjectcodon
dc.subjectenzyme phosphorylation
dc.subjectgene mapping
dc.subjectHuman immunodeficiency virus
dc.subjectmaximum likelihood method
dc.subjectmyristylation
dc.subjectnonhuman
dc.subjectphylogeny
dc.subjectpriority journal
dc.subjectvirus genome
dc.subjectAmino Acid Sequence
dc.subjectChromosome Mapping
dc.subjectDatabases, Genetic
dc.subjectEpitopes
dc.subjectGenes, rev
dc.subjectGenes, tat
dc.subjectGenome, Viral
dc.subjectHIV-1
dc.subjectLikelihood Functions
dc.subjectModels, Genetic
dc.subjectMolecular Sequence Data
dc.subjectPhylogeny
dc.subjectSelection (Genetics)
dc.subjectSequence Alignment
dc.subjectVaccines
dc.subjectVariation (Genetics)
dc.subjectHuman immunodeficiency virus
dc.subjectHuman immunodeficiency virus 1
dc.subjectMacaca
dc.subjectMacaca mulatta
dc.subjectSimian immunodeficiency virus
dc.titleMapping sites of positive selection and amino acid diversification in the HIV genome: An alternative approach to vaccine design?
dc.typeArticle
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