Abstract
The clinical course of HIV-1 varies greatly among infected individuals. Despite extensive research, virus factors associated with slow-progression remain poorly understood. Identification of unique HIV-1 genomic signatures linked to slow-progression remains elusive. We investigated CpG dinucleotide content in HIV-1 envelope gene as a potential virus factor in disease progression. We analysed 1808 HIV-1 envelope gene sequences from three independent longitudinal studies; this included 1280 sequences from twelve typical-progressors and 528 sequences from six slow-progressors. Relative abundance of CpG dinucleotides and relative synonymous codon usage (RSCU) for CpG-containing codons among HIV-1 envelope gene sequences from typical-progressors and slow-progressors were analysed. HIV-1 envelope gene sequences from slow-progressors have high-CpG dinucleotide content and increased number of CpG-containing codons as compared to typical-progressors. Our findings suggest that observed differences in CpG-content between typical-progressors and slow-progressors is not explained by differences in the mononucleotide content. Our results also highlight that the high-CpG content in HIV-1 envelope gene from slow-progressors is observed immediately after seroconversion. Thus CpG dinucleotide content of HIV-1 envelope gene is a potential virus-related factor that is linked to disease progression. The CpG dinucleotide content of HIV-1 envelope gene may help predict HIV-1 disease progression at early stages after seroconversion.
Highlights
Infection with Human Immunodeficiency virus 1 (HIV-1) is a major global problem
Increased CpG-content of HIV-1 env gene is linked to slow disease progression
If the differences in the relative abundance of CpG dinucleotides and the relative synonymous codon usage (RSCU) values of CpG-containing codons are significantly different between typical-progressors and slow-progressors in the early stages of HIV-1 infection, we studied dataset 1, as all HIV-1 infected patients in this study were sampled within the first five months after seroconversion
Summary
Increased CpG-content of HIV-1 env gene is linked to slow disease progression. The differences in the relative abundance of dinucleotides between typical-progressors and slow-progressors for datasets 1, 2 and 3 are shown in Supplementary Figure 1a,b and c respectively. At the first-time point after seroconversion HIV-1 sequences from slow-progressors had higher RSCU values for CpG-containing codons as compared to that from typical-progressors (Figure 5e). Taken together, these findings clearly indicate that the high-CpG content in slow-progressors is seen at the very early stages of HIV-1 infection. The number of clones analyzed is given in parenthesis (d) A scatter plot illustrating CpGO/E ratios in sequences from slow-progressors are not over-lapping with that from the typical-progressors in the first 3 years of after seroconversion (e) Box plots comparing RSCU values of CpG-containing codons in typical-progressors and slow-progressors at the first time point after seroconversion (within 5 months of seroconversion) in dataset 1. We believe that the identification of CpG content of the HIV-1 envelope gene as a potential virus factor in the pathogenesis and disease progression in HIV-1 infected individuals will facilitate a plethora of studies
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