title: Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications.
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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA. georges.teto@unmc.edu.
authors.forename: Georges
authors.initials: G
authors.lastname: Teto
authors.affiliation: Faculty of Medicine and Biomedical Sciences, University of Yaound&#233; I, 1364 Yaound&#233;, Cameroon. yundze.fonsah@gmail.com.|Department of Neurology, Yaound&#233; Central Hospital, 25625 Yaound&#233;, Cameroon. yundze.fonsah@gmail.com.
authors.forename: Julius Y
authors.initials: JY
authors.lastname: Fonsah
authors.affiliation: Faculty of Medicine and Biomedical Sciences, University of Yaound&#233; I, 1364 Yaound&#233;, Cameroon. tayouclaude@yahoo.fr.|Yaound&#233; University Teaching Hospital, 8046 Yaound&#233;, Cameroon. tayouclaude@yahoo.fr.
authors.forename: Claude T
authors.initials: CT
authors.lastname: Tagny
authors.affiliation: Faculty of Medicine and Biomedical Sciences, University of Yaound&#233; I, 1364 Yaound&#233;, Cameroon. dmbanya1@yahoo.co.uk.|Yaound&#233; University Teaching Hospital, 8046 Yaound&#233;, Cameroon. dmbanya1@yahoo.co.uk.
authors.forename: Dora
authors.initials: D
authors.lastname: Mbanya
authors.affiliation: Yaound&#233; University Teaching Hospital, 8046 Yaound&#233;, Cameroon. eminchindap4@yahoo.com.
authors.forename: Emilienne
authors.initials: E
authors.lastname: Nchindap
authors.affiliation: Yaound&#233; University Teaching Hospital, 8046 Yaound&#233;, Cameroon. l.kemmogne@yahoo.com.
authors.forename: Leopoldine
authors.initials: L
authors.lastname: Kenmogne
authors.affiliation: Faculty of Medicine and Biomedical Sciences, University of Yaound&#233; I, 1364 Yaound&#233;, Cameroon. josephfokam@gmail.com.|Sequencing and Bioinformatics Unit, Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, 3077 Yaound&#233;, Cameroon. josephfokam@gmail.com.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fokam
authors.affiliation: HIV-Day Care Service, Yaound&#233; Central Hospital, 87, Yaound&#233;, Cameroon. dmnjamnshi@yahoo.co.uk.
authors.forename: Dora M
authors.initials: DM
authors.lastname: Njamnshi
authors.affiliation: Faculty of Medicine and Biomedical Sciences, University of Yaound&#233; I, 1364 Yaound&#233;, Cameroon. charleskouanfack@yahoo.fr.|HIV-Day Care Service, Yaound&#233; Central Hospital, 87, Yaound&#233;, Cameroon. charleskouanfack@yahoo.fr.
authors.forename: Charles
authors.initials: C
authors.lastname: Kouanfack
authors.affiliation: Faculty of Medicine and Biomedical Sciences, University of Yaound&#233; I, 1364 Yaound&#233;, Cameroon. aknjamnshi@yahoo.co.uk.|Department of Neurology, Yaound&#233; Central Hospital, 25625 Yaound&#233;, Cameroon. aknjamnshi@yahoo.co.uk.
authors.forename: Alfred K
authors.initials: AK
authors.lastname: Njamnshi
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA. gkanmogne@unmc.edu.
authors.forename: Georgette D
authors.initials: GD
authors.lastname: Kanmogne
mesh_terms: D000328:Adult; D002163:Cameroon; D017124:Conserved Sequence; D003430:Cross-Sectional Studies; D000939:Epitopes / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017422:Sequence Analysis, DNA; D055815:Young Adult; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: Cameroon; HIV-1 genetic diversity; HLA binding sites; N-myristoylation; Tat exon-1; amidation; casein kinase-2; phosphorylation