Liang Hao, Wei Min, Chen Zhao, Xing Hui, Zhao Quan-bi, Feng Yi, Guan Qi, Shi Lu-yuan, Shao Yi-ming
School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2003 Jun;17(2):153-8.
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.
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.
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.
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.
鉴定中国HIV-1 B和C主要流行亚型毒株在快速水平传播期间的基因变异情况，并阐明基因变异与选择压力之间的潜在关系。
通过巢式PCR从258例HIV-1感染者的全血中扩增HIV-1 env基因片段后，使用ABI 377 DNA测序仪对PCR产物进行直接测序。选取72株HIV-1 B亚型（n = 37）和C亚型（n = 35）毒株的env V3-V4区域序列进行系统发育分析。此外，使用DIVERGE计算同义替换（Ks）与非同义替换（Ka）的比率。
B亚型毒株V3-V4区域的遗传距离高于C亚型毒株。此外，序列分析显示，B和C亚型毒株的V4区域比V3区域更具变异性。而且，与V3上游区域和C3区域相比，C亚型的V3环变异性较小。两种亚型的整个比对序列的Ks/Ka比率均低于1.0，在B亚型毒株的V3区域和C亚型毒株的V4区域中最低。
B和C亚型毒株的大多数变异发生在V4区域而非V3区域。重要的是，我们的研究首次发现C亚型的V3环比V3上游区域和C3区域更保守。对整个V3-V4区域的Ks/Ka比率计算表明，在中国HIV-1感染人群中病毒快速水平传播期间所经历的显著选择压力可能导致了B亚型毒株V3环和C亚型毒株V4环的变化。这些结果将有助于艾滋病防控政策及正在进行的疫苗研发。
