Relação entre níveis de células T CD4+ e pressão seletiva nos genes env e vif do HIV-1 subtipos B e C

Abstract

Previous studies have shown a direct relationship between levels of CD4+ Tlymphocytes and evolutionary rates of HIV-1 (DIAZ et al, 2008; LEMEY et al, 2007; NOSTROM et al, 2014.). Other factors also affect the variability of the env gene: for example function of neutralizing antibodies - Nabs (FROST et al., 2005), the variation in glycosylation sites; (LEAL et al, 2012 LEAL et al., 2008), binding to target cell receptors (i.e, CD4, CXCR4, CCR5), and also the switch from CCR5 to CXCR4 receptor (MILD et al., 2013). Thus, the relationship between viral levels diversification and CD4 + T cells in the env gene can be circumstantial. The vif gene, on the other hand, it is retained and not subject to bias present in the env gene (i.e, glycosylation sites, etc.). Thus, to study the influence of CD4 + T cells levels in HIV variability, the estimate of the selective regimes was used (Nonsynonymous Substitutions - dN and Synonymous Substitutions - dS) by a codon-based model and phylogenetic analysis of unrelated individuals (inter-host). HIV-1 sequences were used of the not-correlated individuals, obtained from the Los Alamos Database. The sequences were separated into CD4+ levels of categories and then analyzed. The analysis revealed no direct correlation between CD4+ T cell levels and evolutionary rates in gp120 and vif gene from HIV-1, subtypes B and C in a population approach.