Dissecting the Dynamics of HIV-1 Protein Sequence Diversity

Yongli Hu, Paul Thiam Joo Tan, Tin Wee Tan, J. Thomas August, Asif M. Khan

Research output: Contribution to journalArticle

Abstract

The rapid mutation of human immunodeficiency virus-type 1 (HIV-1) and the limited characterization of the composition and incidence of the variant population are major obstacles to the development of an effective HIV-1 vaccine. This issue was addressed by a comprehensive analysis of over 58,000 clade B HIV-1 protein sequences reported over at least 26 years. The sequences were aligned and the 2,874 overlapping nonamer amino acid positions of the viral proteome, each a possible core binding domain for human leukocyte antigen molecules and T-cell receptors, were quantitatively analyzed for four patterns of sequence motifs: (1) "index", the most prevalent sequence; (2) "major" variant, the most common variant sequence; (3) "minor" variants, multiple different sequences, each with an incidence less than that of the major variant; and (4) "unique" variants, each observed only once in the alignment. The collective incidence of the major, minor, and unique variants at each nonamer position represented the total variant population for the position. Positions with more than 50% total variants contained correspondingly reduced incidences of index and major variant sequences and increased minor and unique variants. Highly diverse positions, with 80 to 98% variant nonamer sequences, were present in each protein, including 5% of Gag, and 27% of Env and Nef, each. The multitude of different variant nonamer sequences (i.e. nonatypes; up to 68%) at the highly diverse positions, represented by the major, multiple minor, and multiple unique variants likely supported variants function both in immune escape and as altered peptide ligands with deleterious T-cell responses. The patterns of mutational change were consistent with the sequences of individual HXB2 and C1P viruses and can be considered applicable to all HIV-1 viruses. This characterization of HIV-1 protein mutation provides a foundation for the design of peptide-based vaccines and therapeutics.

Original languageEnglish (US)
Article numbere59994
JournalPloS one
Volume8
Issue number4
DOIs
StatePublished - Apr 4 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Dissecting the Dynamics of HIV-1 Protein Sequence Diversity'. Together they form a unique fingerprint.

  • Cite this

    Hu, Y., Tan, P. T. J., Tan, T. W., August, J. T., & Khan, A. M. (2013). Dissecting the Dynamics of HIV-1 Protein Sequence Diversity. PloS one, 8(4), [e59994]. https://doi.org/10.1371/journal.pone.0059994