| Human Immunodeficiency Virus (HIV) is a member of classs Retroviridae and genus Lentiviridae. Because of the high error rate of reverse transcription, it was generally found that many nucleotides substitution (transition and transvertion), insertion, deletion, and gene segment repeat or inversion in provirus genome, which gives the notable characteristics of HIV high diversity. In addition, continuous, direct and rapid gene mutation happenes in virus genome under the host immune pressures, which adapts HIV virus to host great selective pressures and survive in the enviroment of human body. Furthermore, recombination have been identified as a major mechanism of HIV variation. Intersubtype or intrasubtype recombination can cause most rapid, biggest gene segment changes of the HIV genome, and extraordinarily change the characteristics of virus genetics and biology.The main objective of this research is to study the relationship of gene variation , host selective pressures and antigen epiotpe shifts in GAG nuclear protein of Chinese prevalent HTV-1 subtype B, CRF07-BC, CRF08-BC and CRF01-AE strains collected in the Second National Epidemiology Survey of HIV I hope the results of this paper will contribute to the immunology study of HIV-1 and the ongoing development of AIDS vaccine.Gag gene based phylogenetic analysis of a large number of circulating strains in China , reveales that about 33% HIV-1 prevalent strains belong to subtype Thailand B, and 16% CRF01-AE strains, 36% CRF07-BC , 11% CRF08-BC and 4% other subtype strains. The samples came from all over the country, including HIV intensely and lightly epidemic areas. Number of samples in one area is proportional to the extent of epidemic. So the results generally reflect the HIV-1 prevalent status in our country. The results in this paper also showes that our country's circulating HIV subtype B strains are most close to Thailand strain B.TH.92.92TH014. Surprisingly, the amino acid consensus of Chinese circulating HIV subtype B is completely same with B.TH.92.92TH014 sequence. However, there were 4 amino acids difference (A24S; L47Q; G80D; A88V) with B.CN.RL42,. Similarly, our CRF08-BC strains is most close to standard strain 08_BC.CN98CN006, and a deletion existes from 77 to 80 position (QQKT) in the GAG gene. The other amino acids are same. Our CRF07-BC strains are completely same as standard strain 07_BC.CN97CN001. At last, Our CRF01-AE strainsare genetic similar to 01_AE.TH.90.CM240, 01_AE.JP.93.93JPNH1 and 01_AE.TH.90.CM235-2 respectly, and are more close to 01_AE.TH.90.CM240.Remarkable variation was observed in the flanking region between GAG P17 and P24. The analyses of sequences revealed that many nucleotides substitution (transition and transversion), insertion , deletion, repeat and inversion of gene segment are generally occurred in that region. This kind of mutation rarely caused frameshift reading. So neither the normal translation of P24 region at the downstream nor position for enzyme cut between P17 arid P24 is influenced. It seems that lacking of significant function at this gene region permits the great variation.Ks/Ka ratios shows that, except for CRF08-BC strain, other subtype strains are all under the positive selective pressures at the whole region. Descending order of receiving selective pressures is: CRF01-AE, B, CRF07-BC. Ks/Ka ratio is statistically below 1.0 in P17 region, at the same time, the ks/ka ratio is significantly above 1.0 in the P24 region. From these results we conclude that GAG P17 region is under the positive selective pressures, but P24 region is under the negative selective pressures for Chinese circulating HIV strain except for CRF08-BC strain.The study of antigen epitopes indicate that the conservation of P17 epitopes is lower than that of P24 region distinctly. The more closer to P24 region , the more epitopes are conservative. This trend is consistent with the changes of gene distances and selective pressures in Chinese subtype B strains. The data shows that P17 region seems to... |
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