Abstract
Acquired immune deficiency syndrome (AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV). Two types of HIV have been characterized: HIV-1 and HIV-2. The present study investigated whether evolutionary selection pressure differs between rapid progressor (RP), slow progressor (SP), and long-term non-progressor (LTNP) of HIV-I infected individuals. An unexpected association between the evolutionary rate of substitution in envelope (env) gene and disease progression is observed. Our present study suggests that env genes of LTNP are subject to unusually strong functional constraint with respect to RP. We also observed that the three categories of env genes i.e., RP, SP, and LTNP, had their own characteristic pattern of amino acid usage and SP and LTNP sequences shared similar patterns of amino acid usage different from RP sequences and evolutionary rate significantly influenced the amino acid usage pattern of the three different types of env gene sequences. It was also noted that the evolutionary rate for the glycosylation sites of LTNP and SP sequences were even significantly less than the RP sequences. Comparative analysis on the influence of human host on the three categories of env genes are well correlated with the rates of disease progression suggesting the adaptive strategies of the viruses for successful residence and infection. Host associated selective constraints appeared most relaxed on the RP sequences and strongest in LTNP sequences. The present study clearly portrays how evolutionary selection pressure differs between three categories of env genes i.e., RP, SP, and LTNP. The env genes, coding for the env glycoproteins, experience severe selection constraints from the host due to their constant exposure to the host immune system. In this perspective it might be suggested that env gene evolution occurs mainly by negative selection with the occurrence of mutation that might not reach fixation in the viral population. This work also confers a deeper insight into the crucial effects of host factors that govern the overall progression of HIV infection.
Highlights
Human immunodeficiency viruses (HIVs) are one of the most crucial members of the retroviral family Retroviridae
Phylogenetic analysis was performed to investigate the evolutionary relationship of 264 env gene sequences of HIV-1 subtype B, representing three different categories of patients (RP, slow progressor (SP), and long-term non-progressor (LTNP))
Decreased HIV-1 strain evolution correlates with weaker viral fitness and the inability to evade the host immune system
Summary
Human immunodeficiency viruses (HIVs) are one of the most crucial members of the retroviral family Retroviridae. Due to rapid availability of nucleotide sequence data of viral genes, it is nowadays possible to illustrate a detailed phylogenetic relationship of viruses like HIV. Phylogenetic arrangements of HIV-1 are commonly carried out using nucleotide sequences of different sub-genomic regions of the same HIV-1 genome i.e., gag, pol, and envelope (env). This approach has already revealed unique inter-subtype recombinant forms of virus isolates (McCutchan, 2006). Despite extensive study of sequence variation of env gene of HIV-1, the exact impact of selection in governing the patterns of variation in the env gene still remains somewhat obscure. It has been hypothesized that negative (purifying) selection constraints, operational in HIV-1, execute a crucial role in devising molecular evolutionary patterns of HIV-1 in contrast to positive (diversifying) selection which has been reported to play a minor role (Seo et al, 2002; Drummond et al, 2003)
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