The CpG dinucleotide content of the HIV-1 envelope gene may predict disease progression

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.