Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications
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-Sahar...
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MDPI AG
2016-07-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/8/7/196 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Georges Teto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T23:34:42Z |
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| id | doaj.art-a3d2fba88e5e4a84ae528668b4dcadb3 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-11T23:34:42Z |
| publishDate | 2016-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a3d2fba88e5e4a84ae528668b4dcadb32022-12-22T03:56:59ZengMDPI AGViruses1999-49152016-07-018719610.3390/v8070196v8070196Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional ImplicationsGeorges Teto0Julius Y. Fonsah1Claude T. Tagny2Dora Mbanya3Emilienne Nchindap4Leopoldine Kenmogne5Joseph Fokam6Dora M. Njamnshi7Charles Kouanfack8Alfred K. Njamnshi9Georgette D. Kanmogne10Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USAFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, CameroonFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, CameroonFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, CameroonYaoundé University Teaching Hospital, 8046 Yaoundé, CameroonYaoundé University Teaching Hospital, 8046 Yaoundé, CameroonFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, CameroonHIV-Day Care Service, Yaoundé Central Hospital, 87, Yaoundé, CameroonFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, CameroonFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, 1364 Yaoundé, CameroonDepartment of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USAHIV-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.http://www.mdpi.com/1999-4915/8/7/196CameroonTat exon-1HIV-1 genetic diversityN-myristoylationamidationcasein kinase-2phosphorylationHLA binding sites |
| spellingShingle | 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 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications Viruses Cameroon Tat exon-1 HIV-1 genetic diversity N-myristoylation amidation casein kinase-2 phosphorylation HLA binding sites |
| title | Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications |
| title_full | Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications |
| title_fullStr | Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications |
| title_full_unstemmed | Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications |
| title_short | Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications |
| title_sort | molecular and genetic characterization of hiv 1 tat exon 1 gene from cameroon shows conserved tat hla binding epitopes functional implications |
| topic | Cameroon Tat exon-1 HIV-1 genetic diversity N-myristoylation amidation casein kinase-2 phosphorylation HLA binding sites |
| url | http://www.mdpi.com/1999-4915/8/7/196 |
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