A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism.
A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism.
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DOI：
10.1186/s12977-022-00612-5
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发表时间：
2022-12-13
期刊：
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
--
作者：
我们展示了从1986年初从乌干达各地获得的血清样本中扩增出的109个接近全长的艾滋病毒基因组，据我们所知，这是非洲艾滋病毒流行初期最早和最大的人口样本。在标准方法不成功的情况下，用目标捕获方法从成对的Illumina reads中获得共识序列来扩增HIV物质。与1998 - 1999年较小的“中间”基因组数据集和2007 - 2016年的“现代”基因组数据集相比，D亚型的比例最初明显更高，分别从67%（73/109）下降到57%（26/46）和17% (82/465)（p < 0.0001）。在东非人群研究中，先前已证明D亚型比其他亚型具有更快的疾病进展速度，并且具有更高的使用CXCR4共受体的倾向（“X4趋向性”）；与感染艾滋病的时间缩短有关。在这里，我们发现在所有三个样本时期A1和D亚型之间预测的向性存在显著差异，特别是1986年的样本：66%（53/80）的D亚型环境序列预测为X4向性，而24个A1亚型中没有一个预测为X4向性。我们还分析了亚型间重组包膜区亚型的频率，发现A1亚型在env中过度代表，这表明重组和选择已经将D亚型env从循环中移除。因此，三十年来D亚型频率的减少似乎是对X4趋向性的选择性压力及其较高毒力的结果。最后，我们在V3环的第24位发现了D亚型特异性密码子缺失，这可能解释了D亚型利用X4向性的更高倾向。在线版本包含补充材料，可在10.1186/s12977-022-00612-5获得。
We present 109 near full-length HIV genomes amplified from blood serum samples obtained during early 1986 from across Uganda, which to our knowledge is the earliest and largest population sample from the initial phase of the HIV epidemic in Africa. Consensus sequences were made from paired-end Illumina reads with a target-capture approach to amplify HIV material following poor success with standard approaches. In comparisons with a smaller ‘intermediate’ genome dataset from 1998 to 1999 and a ‘modern’ genome dataset from 2007 to 2016, the proportion of subtype D was significantly higher initially, dropping from 67% (73/109), to 57% (26/46) to 17% (82/465) respectively (p < 0.0001). Subtype D has previously been shown to have a faster rate of disease progression than other subtypes in East African population studies, and to have a higher propensity to use the CXCR4 co-receptor (“X4 tropism”); associated with a decrease in time to AIDS. Here we find significant differences in predicted tropism between A1 and D subtypes in all three sample periods considered, which is particularly striking the 1986 sample: 66% (53/80) of subtype D env sequences were predicted to be X4 tropic compared with none of the 24 subtype A1. We also analysed the frequency of subtype in the envelope region of inter-subtype recombinants, and found that subtype A1 is over-represented in env, suggesting recombination and selection have acted to remove subtype D env from circulation. The reduction of subtype D frequency over three decades therefore appears to be a result of selective pressure against X4 tropism and its higher virulence. Lastly, we find a subtype D specific codon deletion at position 24 of the V3 loop, which may explain the higher propensity for subtype D to utilise X4 tropism. The online version contains supplementary material available at 10.1186/s12977-022-00612-5.
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影响因子：
1.5
作者：
Conroy, Samantha A.;Laeyendecker, Oliver;Quinn, Thomas C.
通讯作者：
Quinn, Thomas C.
DOI：
10.1073/pnas.0708559104
发表时间：
2007-10-30
影响因子：
11.1
作者：
Fraser, Christophe;Hollingsworth, T. Deirdre;Hanage, William P.
通讯作者：
Hanage, William P.
DOI：
10.1097/qad.0000000000000012
发表时间：
2013-11-13
期刊：
AIDS (London, England)
影响因子：
--
作者：
Amornkul PN;Karita E;Kamali A;Rida WN;Sanders EJ;Lakhi S;Price MA;Kilembe W;Cormier E;Anzala O;Latka MH;Bekker LG;Allen SA;Gilmour J;Fast PE;IAVI Africa HIV Prevention Partnership
通讯作者：
IAVI Africa HIV Prevention Partnership
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.
影响因子：
1.5
作者：
DEWOLF, F;HOGERVORST, E;KORBER, B
通讯作者：
KORBER, B