HIV-1 proviral landscape characterization varies by pipeline analysis.
HIV-1 proviral landscape characterization varies by pipeline analysis.
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HIV-1 前病毒景观特征因管道分析而异。
DOI：
10.1002/jia2.25725
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发表时间：
2021-07
影响因子：
6
通讯作者：
Tsibris A
中科院分区：
文献类型：
--
作者：
Ferreira FA;He Q;Banning S;Roberts-Sano O;Wilkins O;Kuritzkes DR;Tsibris A
艾滋病毒在停止抗逆转录病毒治疗后反弹，成为治愈的障碍。为了更好地理解病毒库，已经开发了分析管道，其将前病毒序列分类为完整的或有缺陷的，并进一步确定可能存在的序列缺陷的精确性质。我们研究了不同分析管道对HIV-1前病毒序列表征的影响。我们使用单基因组扩增产生近全长（NFL）HIV-1前病毒DNA序列，定义为长度大于8000个碱基对的扩增子，从接受治疗的HIV-1抑制受试者的外周血单核细胞（PBMC）中分离。对扩增子进行直接下一代单基因组测序，并使用4个HIV-1前病毒表征管道进行分析。将序列表征为完整或缺陷;评估缺陷序列中存在的缺陷数量和类型。为了证实和扩展我们的发现，分析了来自前病毒序列数据库（PSD）的691个前病毒，并使用PSD的ProSeq-IT工具来表征参与者和PSD前病毒。研究了来自13名接受ART治疗的病毒学抑制的HIV受试者的病毒序列。总共产生了693个HIV-1前病毒序列，其中282个是NFL。分析了每位参与者平均53个序列。我们发现，前病毒经常窝藏多种序列缺陷类型（平均值2.7，95%置信区间[CI] 2.5，3.0）;每个管道使用的消除顺序影响分配到每个缺陷类别的前病毒的百分比。这些差异在参与者之间变化，取决于给定前病毒序列中存在的缺陷类别的数量。在表征HIV-1 5′非翻译区（5′ UTR）方面的管道特异性差异导致高估了完整NFL前病毒序列的数量，这一发现在独立PSD分析中得到证实。将四个已发表的管道与ProSeq-IT进行比较发现，ProSeq IT更有可能将前病毒表征为完整的。用于HIV-1前病毒景观分析的管道的选择可能会使缺陷序列的分类产生偏差。为了改善研究组之间前病毒特征的比较，应优先考虑共识消除管道的开发。
HIV rebounds after cessation of antiretroviral therapy, representing a barrier to cure. To better understand the virus reservoir, analysis pipelines have been developed that categorize proviral sequences as intact or defective, and further determine the precise nature of the sequence defects that may be present. We investigated the effects that different analysis pipelines had on the characterization of HIV‐1 proviral sequences. We used single genome amplification to generate near full‐length (NFL) HIV‐1 proviral DNA sequences, defined as amplicons greater than 8000 base pairs in length, isolated from peripheral blood mononuclear cells (PBMC) of treated suppressed participants with HIV‐1. Amplicons underwent direct next‐generation single genome sequencing and were analysed using four HIV‐1 proviral characterization pipelines. Sequences were characterized as intact or defective; defective sequences were assessed for the number and types of defects present. To confirm and extend our findings, 691 proviruses from the Proviral Sequence Database (PSD) were analysed and the ProSeq‐IT tool of the PSD was used to characterize both the participant and PSD proviruses. Virus sequences derived from thirteen ART‐treated virologically suppressed participants with HIV were studied. A total of 693 HIV‐1 proviral sequences were generated, 282 of which were NFL. An average of 53 sequences per participant was analysed. We found that proviruses often harbour multiple sequence defect types (mean 2.7, 95% confidence interval [CI] 2.5, 3.0); the elimination order used by each pipeline affected the percentage of proviruses allotted into each defect category. These differences varied between participants, depending on the number of defect categories present in a given provirus sequence. Pipeline‐specific differences in characterizing the HIV‐1 5′ untranslated region (5′ UTR) led to an overestimation of the number of intact NFL proviral sequences, a finding corroborated in the independent PSD analysis. A comparison of the four published pipelines to ProSeq‐IT found that ProSeq IT was more likely to characterize proviruses as intact. The choice of pipeline used for HIV‐1 provirus landscape analysis may bias the classification of defective sequences. To improve the comparison of provirus characterizations across research groups, the development of a consensus elimination pipeline should be prioritized.
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影响因子：
15.9
作者：
Lee, Guinevere Q.;Orlova-Fink, Nina;Lichterfeld, Mathias
通讯作者：
Lichterfeld, Mathias
DOI：
10.1073/pnas.1609057113
发表时间：
2016-08-02
影响因子：
11.1
作者：
Imamichi, Hiromi;Dewar, Robin L.;Lane, H. Clifford
通讯作者：
Lane, H. Clifford
影响因子：
1.2
作者：
Hiener, Bonnie;Eden, John-Sebastian;Palmer, Sarah
通讯作者：
Palmer, Sarah
影响因子：
64.5
作者：
Ho YC;Shan L;Hosmane NN;Wang J;Laskey SB;Rosenbloom DI;Lai J;Blankson JN;Siliciano JD;Siliciano RF
通讯作者：
Siliciano RF
影响因子：
64.8
作者：
Chun, TW;Carruth, L;Siliciano, RF
通讯作者：
Siliciano, RF