However, in three sufferers there was evidence for segregation of virus quasispecies according to the 12 months of infection, which implies high rate of evolutionary switch and immune selection in these patients [15,60]

However, in three sufferers there was evidence for segregation of virus quasispecies according to the 12 months of infection, which implies high rate of evolutionary switch and immune selection in these patients [15,60]. molecular development of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the env C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2C4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of D-γ-Glutamyl-D-glutamic acid CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity Results The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%), increasing along the course of contamination in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in D-γ-Glutamyl-D-glutamic acid chronic HIV-1 contamination. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and prolonged positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of contamination. Intra-host variance of C2V3C3-specific IgG response over time was inversely associated with the variance in nucleotide and amino acid diversity of the C2V3C3 region. Variance of the C2V3C3-specific IgA response was inversely associated with variance in the number of N-glycosylation sites. Conclusion The evolutionary dynamics of HIV-2 envelope during chronic aviremic contamination is similar to HIV-1 implying that this computer virus should be actively replicating in cellular compartments. Convergent development of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral populace size limiting the number of computer virus escape mutants. The C3 region seems to be a target for IgA antibodies and increasing N-linked glycosylation may prevent HIV-2 envelope acknowledgement by these antibodies. Our results provide new insights into the biology of HIV-2 and its relation with the human host and may have important implications for vaccine design. Background The etiologic brokers of AIDS, HIV-1 and HIV-2, are two unique human lentiviruses with comparable structural and genomic business but sharing only 50% of genetic similarity [1]. Compared to HIV-1, the infection by HIV-2 is usually associated with better prognosis, slower disease progression and transmission, longer latency period and reduced mortality rate [2-6]. Moreover, most HIV-2 patients have normal CD4+ T cell counts and low or undetectable plasmatic viral levels [7,8]. Two possible explanations for these differences may be the slower replication capacity of HIV-2 and a more efficient immune control of HIV-2 [9-13]. The env gene codes for the viral envelope glycoproteins, which are responsible for HIV access into cells [14]. Rapid evolutionary changes and high genetic variability are two major characteristics of the HIV env gene [15]. In HIV-1 contamination, conflicting associations have been reported between disease status and within-patient env gene development. Hence, some studies have shown that genetic diversity and divergence from your infecting strain increase during HIV-1 contamination but become stable or even decrease in the advanced stage of disease, with the lower CD4+ T cell counts and progression to AIDS [16-18]. Other authors have shown that higher genetic diversity and divergence are found in patients with rapid progression to disease than in slow- or non-progressors [19,20]. There is also a GSS positive correlation between viral replication and intrahost HIV-1 development in elite controllers and long-term nonprogressors [21]. The number of studies investigating within-patient HIV-2 molecular development and their association with clinical and immunological development is limited. In one transversal study, we have shown that this genetic diversity of the HIV-2 env may be directly related to the period of contamination [22]. Longitudinal studies performed in Senegal have shown that higher variability in the env V3 region is generally found in patients with faster disease progression to AIDS [23] and that in elite controllers (patients infected for 10 years with normal CD4+ T cell counts without antiretroviral therapy and with low or undetectable viral weight) the rate of env gene diversification may be positively associated with the rate of CD4+ T cell number decrease [24]. Higher rate of molecular development, with predominance of nonsynonymous amino acid substitutions, tends to occur in regions of the HIV-1 env gene submitted to strong selective pressure from your immune system [15,25-28]. A structure D-γ-Glutamyl-D-glutamic acid of particular importance in this process is the V3 loop of the surface glycoprotein which is essential for HIV coreceptor usage [29-32] and for inducing the production of neutralizing and nonneutralizing antibodies in HIV infected individuals [33]. Neutralizing antibody responses, both autologous [34-36] and heterologous [36, 37] may be more common in.