Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications
In: Viruses, Vol 8, Iss 7, p 196 (2016, Jg. 8 (2016), Heft 7, p 196
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Zugriff:
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.
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Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications
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Autor/in / Beteiligte Person: | Teto, Georges ; Fonsah, Julius Y. ; Tagny, Claude T. ; Mbanya, Dora ; Nchindap, Emilienne ; Kenmogne, Leopoldine ; Fokam, Joseph ; Njamnshi, Dora M. ; Kouanfack, Charles ; Njamnshi, Alfred K. ; Kanmogne, Georgette D. |
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Zeitschrift: | Viruses, Vol 8, Iss 7, p 196 (2016, Jg. 8 (2016), Heft 7, p 196 |
Veröffentlichung: | MDPI AG, 2016 |
Medientyp: | academicJournal |
ISSN: | 1999-4915 (print) |
DOI: | 10.3390/v8070196 |
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