| Autor: |
Teto G; Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA. georges.teto@unmc.edu., Fonsah JY; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, Cameroon. yundze.fonsah@gmail.com.; Department of Neurology, Yaoundé Central Hospital, 25625 Yaoundé, Cameroon. yundze.fonsah@gmail.com., Tagny CT; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, Cameroon. tayouclaude@yahoo.fr.; Yaoundé University Teaching Hospital, 8046 Yaoundé, Cameroon. tayouclaude@yahoo.fr., Mbanya D; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, Cameroon. dmbanya1@yahoo.co.uk.; Yaoundé University Teaching Hospital, 8046 Yaoundé, Cameroon. dmbanya1@yahoo.co.uk., Nchindap E; Yaoundé University Teaching Hospital, 8046 Yaoundé, Cameroon. eminchindap4@yahoo.com., Kenmogne L; Yaoundé University Teaching Hospital, 8046 Yaoundé, Cameroon. l.kemmogne@yahoo.com., Fokam J; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, Cameroon. josephfokam@gmail.com.; Sequencing and Bioinformatics Unit, Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, 3077 Yaoundé, Cameroon. josephfokam@gmail.com., Njamnshi DM; HIV-Day Care Service, Yaoundé Central Hospital, 87, Yaoundé, Cameroon. dmnjamnshi@yahoo.co.uk., Kouanfack C; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, Cameroon. charleskouanfack@yahoo.fr.; HIV-Day Care Service, Yaoundé Central Hospital, 87, Yaoundé, Cameroon. charleskouanfack@yahoo.fr., Njamnshi AK; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, Cameroon. aknjamnshi@yahoo.co.uk.; Department of Neurology, Yaoundé Central Hospital, 25625 Yaoundé, Cameroon. aknjamnshi@yahoo.co.uk., Kanmogne GD; Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA. gkanmogne@unmc.edu. |
| Abstrakt: |
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. |
