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Viruses 2016, 8(7), 196; doi:10.3390/v8070196

Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications

1
Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA
2
Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, Cameroon
3
Department of Neurology, Yaoundé Central Hospital, 25625 Yaoundé, Cameroon
4
Yaoundé University Teaching Hospital, 8046 Yaoundé, Cameroon
5
Sequencing and Bioinformatics Unit, Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, 3077 Yaoundé, Cameroon
6
HIV-Day Care Service, Yaoundé Central Hospital, 87, Yaoundé, Cameroon
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 6 May 2016 / Revised: 24 June 2016 / Accepted: 12 July 2016 / Published: 18 July 2016
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [7149 KB, uploaded 18 July 2016]   |  

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. View Full-Text
Keywords: Cameroon; Tat exon-1; HIV-1 genetic diversity; N-myristoylation; amidation; casein kinase-2; phosphorylation; HLA binding sites Cameroon; Tat exon-1; HIV-1 genetic diversity; N-myristoylation; amidation; casein kinase-2; phosphorylation; HLA binding sites
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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. Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Viruses 2016, 8, 196.

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