Molecular and genetic characterization of HIV-1 tat exon-1 gene from cameroon shows conserved tat HLA-binding epitopes: Functional implications

Georges Teto, Julius Y. Fonsah, Claude T. Tagny, Dora Mbanya, Emilienne Nchindap, Leopoldine Kenmogne, Joseph Fokam, Dora M. Njamnshi, Charles Kouanfack, Alfred K. Njamnshi, Georgette D. Kanmogne

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

HIV-1 Tat plays a critical role in viral transactivation. Subtype-B Tat has potential use as a therapeutic vaccine. However, viral genetic diversity and population genetics would significantly impact the efficacy of such a vaccine. Over 70% of the 37-million HIV-infected individuals are in sub-Saharan Africa (SSA) and harbor non-subtype-B HIV-1. Using specimens from 100 HIV-infected Cameroonians, we analyzed the sequences of HIV-1 Tat exon-1, its functional domains, post-translational modifications (PTMs), and human leukocyte antigens (HLA)-binding epitopes. Molecular phylogeny revealed a high genetic diversity with nine subtypes, CRF22_01A1/CRF01_AE, and negative selection in all subtypes. Amino acid mutations in Tat functional domains included N24K (44%), N29K (58%), and N40K (30%) in CRF02_AG, and N24K in all G subtypes. Motifs and phosphorylation analyses showed conserved amidation, N-myristoylation, casein kinase-2 (CK2), serine and threonine phosphorylation sites. Analysis of HLA allelic frequencies showed that epitopes for HLAs A* 0205, B* 5301, Cw* 0401, Cw* 0602, and Cw* 0702 were conserved in 58%-100% of samples, with B* 5301 epitopes having binding affinity scores > 100 in all subtypes. This is the first report of N-myristoylation, amidation, and CK2 sites in Tat; these PTMs and mutations could affect Tat function. HLA epitopes identified could be useful for designing Tat-based vaccines for highly diverse HIV-1 populations, as in SSA.

Original languageEnglish (US)
Article number196
JournalViruses
Volume8
Issue number7
DOIs
StatePublished - Jul 18 2016

Keywords

  • Amidation
  • Cameroon
  • Casein kinase-2
  • HIV-1 genetic diversity
  • HLA binding sites
  • N-myristoylation
  • Phosphorylation
  • Tat exon-1

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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    Teto, G., Fonsah, J. Y., Tagny, C. T., Mbanya, D., Nchindap, E., Kenmogne, L., Fokam, J., Njamnshi, D. M., Kouanfack, C., Njamnshi, A. K., & Kanmogne, G. D. (2016). Molecular and genetic characterization of HIV-1 tat exon-1 gene from cameroon shows conserved tat HLA-binding epitopes: Functional implications. Viruses, 8(7), [196]. https://doi.org/10.3390/v8070196