Mapping sites of positive selection and amino acid diversification in the HIV genome: An alternative approach to vaccine design?
Date
2004
Authors
De Oliveira T.
Salemi M.
Gordon M.
Vandamme A.-M.
Van Rensburg E.J.
Engelbrecht S.
Coovadia H.M.
Cassol S.
Journal Title
Journal ISSN
Volume Title
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Abstract
A 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.
Description
Keywords
amino acid, casein kinase II, epitope, Human immunodeficiency virus vaccine, immediate early protein, peptide, Rev protein, transactivator protein, virus envelope protein, virus protein, amino acid sequence, amino acid substitution, antigenicity, article, codon, enzyme phosphorylation, gene mapping, Human immunodeficiency virus, maximum likelihood method, myristylation, nonhuman, phylogeny, priority journal, virus genome, Amino Acid Sequence, Chromosome Mapping, Databases, Genetic, Epitopes, Genes, rev, Genes, tat, Genome, Viral, HIV-1, Likelihood Functions, Models, Genetic, Molecular Sequence Data, Phylogeny, Selection (Genetics), Sequence Alignment, Vaccines, Variation (Genetics), Human immunodeficiency virus, Human immunodeficiency virus 1, Macaca, Macaca mulatta, Simian immunodeficiency virus
Citation
Genetics
167
3
167
3