In-Depth Characterization of Full-Length Archived Viral Genomes after Nine Years of Posttreatment HIV Control.
In-Depth Characterization of Full-Length Archived Viral Genomes after Nine Years of Posttreatment HIV Control.
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DOI：
10.1128/spectrum.03267-22
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发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
在没有抗逆转录病毒治疗的情况下控制人类免疫缺陷病毒1型(HIV-1)感染的研究中，后处理控制器(PTCs)是HIV缓解的典范。为了更好地了解他们的控制机制，我们比较了8个PTC(治疗中断后的中位数为9.4 年)与13个自然艾滋病毒感染控制组(HIC)(感染的中位数为18 年)以及在初次艾滋病毒感染(PHI；n = 8)或慢性艾滋病毒感染(CHI；n = 6)期间开始接受有效抗逆转录病毒治疗的个体的艾滋病毒血库。这一特征是通过单基因组扩增和深度测序进行的。反映过去病毒复制历史的前病毒多样性，在PTC、PHI和无菌HICs中低于Bipper HICs和CHI。PTC组前体池中完整前体组和缺陷前体组的比例与其他组无显著差异。当观察每百万外周血单个核细胞(PBMC)中的前病毒数量时，他们的完整前病毒数量与其他组相似，但缺陷前病毒数量比CHI更少，这表明这些形式在艾滋病毒发病机制中发挥了作用。两个HIC，但没有一个PTC只携带nef缺失的前病毒；这些减毒株可能有助于这些参与者的病毒控制。我们首次发现，在治疗中断很长一段时间后，PTC中存在完整的前病毒和低病毒多样性，并且在随后的样本中没有前病毒准种的进化。这反映了随着时间的推移，复制残留量较低。需要更多的数据来证实这些结果。重要性大多数艾滋病毒携带者需要抗逆转录病毒治疗来控制他们的感染，并在治疗中断的情况下经历病毒复发，因为病毒库(前病毒)持续存在。了解到前病毒是非常多样化的，并且在接受治疗的个体中大多数是缺陷的，我们的目标是描述治疗后控制者(PTCs)的HIV血库，这是一种罕见的非药物缓解模式，与自发控制者和接受治疗的个体进行比较。在治疗中断后的中位时间为9 年，这在文献中是史无前例的，我们表明PTC和其他个体之间完整的前病毒的比例和数量是相似的。与2/7的自发控制者不同的是，在PTC中没有观察到这种情况，而是只含有nef缺失的前病毒，这是有助于它们控制的减毒株。此外，尽管存在完整的前病毒，但PTC的病毒遗传多样性很低，其储存库没有进化，表明残留复制非常低。
In the search for control of human immunodeficiency virus type 1 (HIV-1) infection without antiretroviral therapy, posttreatment controllers (PTCs) are models of HIV remission. To better understand their mechanisms of control, we characterized the HIV blood reservoirs of 8 PTCs (median of 9.4 years after treatment interruption) in comparison with those of 13 natural HIV infection controllers (HICs) (median of 18 years of infection) and with those of individuals receiving efficient antiretroviral therapy initiated during either primary HIV infection (PHIs; n = 8) or chronic HIV infection (CHIs; n = 6). This characterization was performed with single-genome amplification and deep sequencing. The proviral diversity, which reflects the history of past viral replication, was lower in the PTCs, PHIs, and aviremic HICs than in the blipper HICs and CHIs. The proportions of intact and defective proviruses among the proviral pool in PTCs were not significantly different from those of other groups. When looking at the quantities of proviruses per million peripheral blood mononuclear cells (PBMCs), they had similar amounts of intact proviruses as other groups but smaller amounts of defective proviruses than CHIs, suggesting a role of these forms in HIV pathogenesis. Two HICs but none of the PTCs harbored only proviruses with deletion in nef; these attenuated strains could contribute to viral control in these participants. We show, for the first time, the presence of intact proviruses and low viral diversity in PTCs long after treatment interruption, as well as the absence of evolution of the proviral quasispecies in subsequent samples. This reflects low residual replication over time. Further data are necessary to confirm these results. IMPORTANCE Most people living with HIV need antiretroviral therapy to control their infection and experience viral relapse in case of treatment interruption, because of viral reservoir (proviruses) persistence. Knowing that proviruses are very diverse and most of them are defective in treated individuals, we aimed to characterize the HIV blood reservoirs of posttreatment controllers (PTCs), rare models of drug-free remission, in comparison with spontaneous controllers and treated individuals. At a median time of 9 years after treatment interruption, which is unprecedented in the literature, we showed that the proportions and quantities of intact proviruses were similar between PTCs and other individuals. Unlike 2/7 spontaneous controllers who harbored only nef-deleted proviruses, which are attenuated strains, which could contribute to their control, no such case was observed in PTCs. Furthermore, PTCs displayed low viral genetic diversity and no evolution of their reservoirs, indicating very low residual replication, despite the presence of intact proviruses.
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影响因子：
6.4
作者：
Casado, Concepcion;Marrero-Hernandez, Sara;Lopez-Galindez, Cecilio
通讯作者：
Lopez-Galindez, Cecilio
影响因子：
6.4
作者：
Avettand-Fenoel, Veronique;Blanche, Stephane;Buseyne, Florence
通讯作者：
Buseyne, Florence
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：
64.5
作者：
Einkauf KB;Osborn MR;Gao C;Sun W;Sun X;Lian X;Parsons EM;Gladkov GT;Seiger KW;Blackmer JE;Jiang C;Yukl SA;Rosenberg ES;Yu XG;Lichterfeld M
通讯作者：
Lichterfeld M
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.