Next Article in Journal
Human Papillomavirus and Tonsillar and Base of Tongue Cancer
Previous Article in Journal
The Cryptophlebia Leucotreta Granulovirus—10 Years of Commercial Field Use
Open AccessArticle

Selection Pressure in CD8+ T-cell Epitopes in the pol Gene of HIV-1 Infected Individuals in Colombia. A Bioinformatic Approach

1
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, 050010, Colombia
2
Programa de Estudio y Control de Enfermedades Tropicales—PECET, Universidad de Antioquia, Medellín, 050010, Colombia
3
Centro de Análisis Molecular, Bogotá D.C., 111156, Colombia
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Viruses 2015, 7(3), 1313-1331; https://doi.org/10.3390/v7031313
Received: 17 September 2014 / Revised: 23 February 2015 / Accepted: 24 February 2015 / Published: 20 March 2015
(This article belongs to the Section Animal Viruses)
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. View Full-Text
Keywords: human immunodeficiency virus; positive selection; epitopes; docking; CD8+ T-cells human immunodeficiency virus; positive selection; epitopes; docking; CD8+ T-cells
Show Figures

Figure 1

MDPI and ACS Style

Acevedo-Sáenz, L.; Ochoa, R.; Rugeles, M.T.; Olaya-García, P.; Velilla-Hernández, P.A.; Diaz, F.J. Selection Pressure in CD8+ T-cell Epitopes in the pol Gene of HIV-1 Infected Individuals in Colombia. A Bioinformatic Approach. Viruses 2015, 7, 1313-1331.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Search more from Scilit
 
Search
Back to TopTop