The genetic interaction between HIV and the antibody repertoire

The genetic interaction between HIV and the antibody repertoire
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HIV 和抗体库之间的遗传相互作用

DOI:
10.1101/646968
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发表时间:
2019
期刊:
bioRxiv
影响因子:
--
通讯作者:
Ryan D. Hernandez
Ryan D. Hernandez
中科院分区:
--
文献类型:
--
作者:
N. Strauli;Emily Fryer;Olivia Pham;M. Abdel;S. Facente;C. Pilcher;P. Pennings;S. Pillai;Ryan D. Hernandez

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人类免疫缺陷病毒(human immunodeficiency virus,HIV)与抗体库(antibody repertoire,AbR)在慢性感染过程中的相互作用可以为HIV疫苗研究提供重要信息,但尚未在系统水平上得到很好的表征。我们对10名艾滋病毒感染者、抗逆转录病毒(ART)初治者的HIV群体和AbR进行了深度测序,每个人有10-20个纵向样本,时间跨度为4-14年。我们的无偏测序方法鉴定了显示与自体HIV群体相互作用的证据的AbR分区。我们发现,这些HIV相关的分区富集已知的HIV广泛中和抗体(bnAb)的V基因片段,这表明可以通过时间序列遗传数据来识别AbR的HIV应答组分。尽管有证据表明在亚群水平上存在较大规模的AbR/HIV相互作用,但我们几乎没有发现共同进化的证据。这表明,共同进化要么是罕见的,要么是难以检测的,这对疫苗设计具有重要意义。
The interaction between human immunodeficiency virus (HIV) and the antibody repertoire (AbR) during chronic infection can provide important information for HIV vaccine research, yet has not been well-characterized on a systems level. We deeply sequenced the HIV population and the AbR of ten HIV-infected, antiretroviral (ART)-naïve individuals, each with 10-20 longitudinal samples spanning 4-14 years. Our unbiased sequencing approach identified partitions of AbRs showing evidence of interaction with autologous HIV populations. We show that these HIV-associated partitions are enriched for the V gene segments of known HIV broadly neutralizing antibodies (bnAbs), indicating that the HIV-responding component of the AbR can be identified via time-series genetic data. Despite this evidence for larger-scale AbR/HIV interactions at the sub-population level, we found little to no evidence for coevolution. This suggests that coevolution is either rare, or hard to detect, which has important vaccine design implications.
DOI: 10.1371/journal.ppat.1002529
发表时间: 2012
期刊: PLoS pathogens
影响因子: 6.7
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