6 results on '"Liliana Acevedo"'
Search Results
2. Polyfunctional CD8+ T-Cell Response to Autologous Peptides from Protease and Reverse Transcriptase of HIV-1 Clade B
- Author
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Liliana Acevedo-Sáenz, Carlos J. Montoya, Paula A. Velilla, and Federico Perdomo-Celis
- Subjects
0301 basic medicine ,Adult ,Male ,Genotype ,HIV Antigens ,medicine.medical_treatment ,Viremia ,HIV Infections ,Biology ,CD8-Positive T-Lymphocytes ,Colombia ,Epitope ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,HIV Protease ,Virology ,medicine ,Cytotoxic T cell ,Humans ,Immunologic Factors ,Protease ,Middle Aged ,medicine.disease ,Flow Cytometry ,Reverse transcriptase ,HIV Reverse Transcriptase ,030104 developmental biology ,Infectious Diseases ,HIV-1 ,Female ,Ex vivo ,CD8 ,030215 immunology - Abstract
Background: : The diversity of the HIV proteome influences the cellular response and development of an effective vaccine, particularly due to the generation of viral variants with mutations located within CD8+ T-cell epitopes. These mutations can affect the recognition of the epitopes, that may result in the selection of HIV variants with mutated epitopes (autologous epitopes) and different CD8+ T-cell functional profiles. Objective:: To determine the phenotype and functionality of CD8+ T-cell from HIV-infected Colombian patients in response to autologous and consensus peptides derived from HIV-1 clade B protease and reverse transcriptase (RT). Methods:: By flow cytometry, we compared the ex vivo CD8+ T-cell responses from HIV-infected patients to autologous and consensus peptides derived from HIV-1 clade B protease and RT, restricted by HLA-B*35, HLA-B*44 and HLA-B*51 alleles. Results:: Although autologous peptides restricted by HLA-B*35 and HLA-B*44 did not show any differences compared with consensus peptides, we observed the induction of a higher polyfunctional profile of CD8+ T-cells by autologous peptides restricted by HLA-B*51, particularly by the production of interferon-γ and macrophage inflammatory protein-1β. The response by different memory CD8+ T-cell populations was comparable between autologous vs. consensus peptides. In addition, the magnitude of the polyfunctional response induced by the HLA-B*51-restricted QRPLVTIRI autologous epitope correlated with low viremia. Conclusion:: Autologous peptides should be considered for the evaluation of HIV-specific CD8+ Tcell responses and to reveal some relevant epitopes that could be useful for therapeutic strategies aiming to promote polyfunctional CD8+ T-cell responses in a specific population of HIV-infected patients.
- Published
- 2019
3. Cytotoxic CD4
- Author
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Alexandra, Sanchez-Martinez, Federico, Perdomo-Celis, Liliana, Acevedo-Saenz, Maria T, Rugeles, and Paula A, Velilla
- Subjects
CD4-Positive T-Lymphocytes ,Phenotype ,T-Lymphocyte Subsets ,Disease Progression ,Humans ,Apoptosis ,HIV Infections ,CD8-Positive T-Lymphocytes ,Antiviral Agents ,T-Lymphocytes, Cytotoxic - Abstract
Classically, CD4
- Published
- 2019
4. Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
- Author
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David Arcia, Juan C. Hernandez, Paula A. Velilla, Liliana Acevedo-Sáenz, Rodrigo Ochoa, Francisco J. Díaz, and Cristiam M. Alvarez
- Subjects
0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,Epitopes, T-Lymphocyte ,HIV Infections ,Biology ,Colombia ,Microbiology ,gag Gene Products, Human Immunodeficiency Virus ,Epitope ,Virus ,03 medical and health sciences ,Structure-Activity Relationship ,Genetics ,Immune Tolerance ,Humans ,Genetic variability ,Allele ,Selection, Genetic ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,Histocompatibility Antigens Class I ,Wild type ,Viral Load ,HLA-B ,HLA-A ,CD4 Lymphocyte Count ,030104 developmental biology ,Infectious Diseases ,Phenotype ,Mutation ,HIV-1 ,RNA, Viral ,Viral load - Abstract
The introduction of highly active antiretroviral therapy (HAART) has significantly improved life expectancy of HIV-infected patients; nevertheless, it does not eliminate the virus from hosts, so a cure for this infection is crucial. Some strategies have employed the induction of anti-HIV CD8+ T cells. However, the high genetic variability of HIV-1 represents the biggest obstacle for these strategies, since immune escape mutations within epitopes restricted by Human Leukocyte Antigen class I molecules (HLA-I) abrogate the antiviral activity of these cells. We used a bioinformatics pipeline for the determination of such mutations, based on selection pressure and docking/refinement analyses. Fifty HIV-1 infected patients were recruited; HLA-A and HLA-B alleles were typified using sequence-specific oligonucleotide approach, and viral RNA was extracted for the amplification of HIV-1 gag, which was bulk sequenced and aligned to perform selection pressure analysis, using Single Likelihood Ancestor Counting (SLAC) and Fast Unconstrained Bayesian Approximation (FUBAR) algorithms. Positively selected sites were mapped into HLA-I-specific epitopes, and both mutated and wild type epitopes were modelled using PEP-FOLD. Molecular docking and refinement assays were carried out using AutoDock Vina 4 and FlexPepDock. Five positively selected sites were found: S54 at HLA-A*02 GC9, T84 at HLA-A*02 SL9, S125 at HLA-B*35 HY9, S173 at HLA-A*02/B*57 KS12 and I223 at HLA-B*35 HA9. Although some mutations have been previously described as immune escape mutations, the majority of them have not been reported. Molecular docking/refinement analysis showed that one combination of mutations at GC9, one at SL9, and eight at HY9 epitopes could act as immune escape mutations. Moreover, HLA-A*02-positive patients harbouring mutations at KS12, and HLA-B*35-positive patients with mutations at HY9 have significantly higher plasma viral loads than patients lacking such mutations. Thus, HLA-A and -B alleles could be shaping the genetic diversity of HIV-1 through the selection of potential immune escape mutations.
- Published
- 2018
5. Role of CD8
- Author
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David, Arcia, Liliana, Acevedo-Sáenz, María Teresa, Rugeles, and Paula A, Velilla
- Subjects
Host-Pathogen Interactions ,Mutation ,Epitopes, T-Lymphocyte ,Humans ,HIV Infections ,Genetic Fitness ,CD8-Positive T-Lymphocytes ,Selection, Genetic ,Immune Evasion - Abstract
Human immunodeficiency virus type-1 (HIV-1) infection represents one of the biggest public health problems worldwide. The immune response, mainly the effector mechanisms mediated by CD8
- Published
- 2016
6. Selection pressure in CD8⁺ T-cell epitopes in the pol gene of HIV-1 infected individuals in Colombia. A bioinformatic approach
- Author
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Francisco J. Díaz, Rodrigo Ochoa, Paula Andrea Velilla-Hernández, María Teresa Rugeles, Liliana Acevedo-Sáenz, and Patricia Olaya-García
- Subjects
CD8+ T-cells ,lcsh:QR1-502 ,Mutation, Missense ,Epitopes, T-Lymphocyte ,HIV Infections ,Human leukocyte antigen ,Biology ,CD8-Positive T-Lymphocytes ,Colombia ,lcsh:Microbiology ,Epitope ,Article ,Genetic drift ,HLA Antigens ,positive selection ,Virology ,Drug Resistance, Viral ,Humans ,Genetic variability ,Binding site ,Selection, Genetic ,Genetics ,Binding Sites ,human immunodeficiency virus ,Computational Biology ,epitopes ,Reverse transcriptase ,HIV Reverse Transcriptase ,Infectious Diseases ,Anti-Retroviral Agents ,Docking (molecular) ,pol Gene Products, Human Immunodeficiency Virus ,docking ,HIV-1 ,Synonymous substitution ,Protein Binding - Abstract
One of the main characteristics of the human immunodeficiency virus is its genetic variability and rapid adaptation to changing environmental conditions. This variability, resulting from the lack of proofreading activity of the viral reverse transcriptase, generates mutations that could be fixed either by random genetic drift or by positive selection. Among the forces driving positive selection are antiretroviral therapy and CD8+ T-cells, the most important immune mechanism involved in viral control. Here, we describe mutations induced by these selective forces acting on the pol gene of HIV in a group of infected individuals. We used Maximum Likelihood analyses of the ratio of non-synonymous to synonymous mutations per site (dN/dS) to study the extent of positive selection in the protease and the reverse transcriptase, using 614 viral sequences from Colombian patients. We also performed computational approaches, docking and algorithmic analyses, to assess whether the positively selected mutations affected binding to the HLA molecules. We found 19 positively-selected codons in drug resistance-associated sites and 22 located within CD8+ T-cell epitopes. A high percentage of mutations in these epitopes has not been previously reported. According to the docking analyses only one of those mutations affected HLA binding. However, algorithmic methods predicted a decrease in the affinity for the HLA molecule in seven mutated peptides. The bioinformatics strategies described here are useful to identify putative positively selected mutations associated with immune escape but should be complemented with an experimental approach to define the impact of these mutations on the functional profile of the CD8+ T-cells.
- Published
- 2014
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