Objective: To identify genetic variation of HIV-1 predominant subtype B and C strains in China during rapid horizontal transmission and to elucidate the potential relationship between genetic variation and selective pressure.
Methods: After the fragments of HIV-1 env gene were amplified by nested-PCR from the whole blood of 258 HIV-1 infected individuals, PCR products were directly sequenced using ABI 377 DNA sequencer. The sequences covering env V3-V4 region of 72 HIV-1 subtype B(n=37) and C(n=35) strains were selected for phylogenetic analysis. In addition, the ratios of synonymous (Ks) substitutions per nonsynonymous (Ka) substitutions were calculated using DIVERGE.
Results: The genetic distances of the V3-V4 region of subtype B strains were higher than that of subtype C strains. Furthermore, sequence analysis revealed that the V4 region was more variable than the V3 region for both subtype B and C strains. What's more, the V3 loop was less variable compared with the V3 upstream region and C3 region for subtype C Ks/Ka ratios of the entire aligned sequence of the two subtypes were below 1 0, with the lowest values found in the V3 region of subtype B strain and the V4 region of subtype C strain.
Conclusions: The majority of variation in both subtypes B and C strains occurred in the V4 rather than the V3 region. It is important that our study found for the first time the V3 loop was more conservative than the V3 upstream region and C3 region for subtype C. Calculations of the Ks/Ka ratios throughout the V3-V4 region demonstrate that significant selective pressures experienced during the rapid horizontal spread of the virus in the Chinese HIV-1 infected population may have directed change in the V3 loop for the subtype B strain and the V4 loop for the subtype C strain. These results will contribute to the policy of AIDS prevention and control and the ongoing development vaccine.