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在巴西患有HIV-1长期感染且临床分期不明的献血者中频繁检测到利用CXCR4的病毒:大规模平行测序数据分析

Frequent detection of CXCR4-using viruses among Brazilian blood donors with HIV-1 long-standing infection and unknown clinical stage: Analysis of massive parallel sequencing data.

作者信息

Pessôa Rodrigo, Sanabani Sabri S

机构信息

Department of Pathology, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.

出版信息

Data Brief. 2015 Dec 17;6:267-74. doi: 10.1016/j.dib.2015.12.008. eCollection 2016 Mar.

Abstract

The determination of viral tropism is critically important and highly recommended to guide therapy with the CCR5 antagonist, which does not inhibit the effect of X4-tropic viruses. Here, we report the prevalence of HIV-1×4 HIV strains in 84 proviral DNA massively parallel sequencing "MPS" data from well-defined non-recently infected first-time Brazilian blood donors. The MPS data covering the entire V3 region of the env gene was extracted from our recently generated HIV-1 genomes sequenced by a paired-end protocol (Illumina). Of the 84 MPS data samples, 63 (75%) were derived from donors with long-standing infection and 21 (25%) were lacking stage information. HIV-1 tropism was inferred using Geno2pheno (g2p) [454] algorithm (FPR=1%, 2.5%, and 3.75%). Among the 84 data samples for which tropism was defined by g2p2.5%, 13 (15.5%) participants had detectable CXCR4-using viruses in their MPS reads. Mixed infections with R5 and X4 were observed in 11.9% of the study subjects and minority X4 viruses were detected in 7 (8.3%) of participants. Nine of the 63 (14.3%) subjects with LS infection were predicted by g2p 2.5% to harbor proviral CXCR4-using viruses. Our findings of a high proportion of blood donors (15.5%) harboring CXCR4-using viruses in PBMCs may indicate that this phenomenon is common. These findings may have implications for clinical and therapeutic aspects and may benefit individuals who plan to receive CCR5 antagonists.

摘要

确定病毒嗜性至关重要,强烈建议以此指导CCR5拮抗剂的治疗,因为该拮抗剂不会抑制X4嗜性病毒的作用。在此,我们报告了来自明确的非近期感染的首次巴西献血者的84个前病毒DNA大规模平行测序(MPS)数据中HIV-1 X4病毒株的流行情况。覆盖env基因整个V3区域的MPS数据是从我们最近通过双末端协议(Illumina)测序生成的HIV-1基因组中提取的。在84个MPS数据样本中,63个(75%)来自长期感染的献血者,21个(25%)缺乏分期信息。使用Geno2pheno(g2p)[454]算法(假阳性率=1%、2.5%和3.75%)推断HIV-1嗜性。在通过g2p 2.5%定义嗜性的84个数据样本中,13名(15.5%)参与者的MPS读数中可检测到使用CXCR4的病毒。在11.9%的研究对象中观察到R5和X4的混合感染,7名(8.3%)参与者检测到少数X4病毒。63名长期感染的受试者中有9名(14.3%)通过g2p 2.5%预测携带使用前病毒CXCR4的病毒。我们发现相当比例的献血者(15.5%)外周血单核细胞中携带使用CXCR4的病毒,这可能表明这种现象很常见。这些发现可能对临床和治疗方面有影响,可能会使计划接受CCR5拮抗剂治疗的个体受益。

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