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- Title
Molecular characterization and phylogenetic analysis of HIV-1 Tat and Rev proteins from antiretroviral therapy-naïve Mexican infected individuals.
- Authors
Fuentes-Romero, Luis León; Alvarado-Estrada, Yesica; Rosas-Alquicira, Graciela; Vergara-Mendoza, Moisés; Viveros-Rogel, Mónica
- Abstract
To modulate viral replication in early infection, HIV directs the synthesis of Tat and Rev regulatory proteins at the transcriptional and post-transcriptional level respectively. We provided a detailed molecular analysis of 29 Tat and Rev protein sequences derived from PBMCs obtained from 22 antiretroviral therapy-naïve Mexican HIV-1 infected individuals. Of the 29 sequences, seven were sampled from the same patient at different times, spanning between 1 and 3 years between samples, to evaluate genetic evolution. The 3D-protein molecular structure, evolutionary relationships among populations and phylogeny were evaluated. Tajima’s-D test was used to assess genetic diversity. Tat and Rev showed a low diversity (Tajima’s D value: Rev = 0.811, Tat = 0.758) and reduced genetic distance (Kimura 2-parameters: Rev = 0.109, Tat = 0.067). Low intraindividual evolutionary divergence was found in samples obtained from the same patient at different times (Poisson-correction model: Rev = 0.14, Tat = 0.13) with respect to interindividual divergence (Rev = 0.174, Tat = 0.170). Q54R mutation which decrease Tat-TAR binding affinity was found in 2/29 sequences. RGD motif which is associated with Tat-mediated LTR-promoter activity was replaced by QGD in a sample of non-progressor to AIDS. High polymorphism in Rev oligomerization domain was observed and stop codons were identified in turn region and C-term domain. The 3D protein analysis showed a conserved structure of Tat and Rev proteins. Tajima’s D test showed a population expansion on both proteins indicating a recent selective pressure attributable to the immune system or transcriptase reverse error prone. Broadening our knowledge of the genetic diversity of HIV-1 regulatory genes is critical to develop novel therapeutic anti-HIV-1 strategies.
- Publication
Veterinaria México OA, 2024, Vol 11, p21
- ISSN
2448-6760
- Publication type
Article
- DOI
10.22201/fmvz.24486760e.2024.1305