Characterization of variable regions of the gp120 protein from HIV-1 subtype C virus variants obtained from individuals at different disease stages in sub-Saharan Africa.

Background: The development of a vaccine against HIV/AIDS capable of preventing virus infection has been hampered by the HIV envelope (Env) heterogeneity that makes it difficult to induce neutralizing antibodies against Env proteins from different HIV clades. Several studies have indicated that gp120 Env protein sequence tends to change considerably during the course of HIV disease which allows the virus to escape the immune responses. In order to define gp120 sequence changes, we have characterized the V1, V2, V4 and V5 variable regions of gp120 variants from 72 HIV-1-clade-C-infected subjects from South Africa and Swaziland, which were naive to antiretroviral (ARV) therapy and at different disease stages. Sequence characteristics, such as aminoacid sequence length, presence of Putative N-Glycosylation Sites (PNGSs) and electric charge were investigated. Methods: According to the Avidity Index value and CD4+ T cell count, patients were classified for disease stage in three groups: recent, chronic and late stage, each one comprised of 24 patients. The V1 to V5 Env variable regions were directly PCR amplified from plasma virus RNA and sequenced. Results: A significant increase in the amino acid sequence length of V1 and V4 domains, and a corresponding increase of the shifting PNGSs were observed in the HIV variants obtained from individuals at chronic stage of disease, as compared to the recent infection group. Finally, a significant increase of the net electric positive charge of the V5 loop was found in the HIV variants from the group of subjects with late disease, as compared to the chronic disease group. Conclusion: We conclude that changes in sequence length, glycosylation pattern and net electrical charge in the variable V1, V4 and V5 regions of gp120 occur in the course of HIV infection, possibly in response to the pressure of the host immune response.