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检测和分子特征分析尿路上皮 HIV-1 群体。

Detection and molecular characterization of urinary tract HIV-1 populations.

机构信息

Department of Pathology, Faculty of Medicine, National University of Science & Technology, Ascot, P. O Box AC 939, Bulawayo, Zimbabwe.

Department of Medical Virology, University of Pretoria, Pretoria, South Africa.

出版信息

Ann Clin Microbiol Antimicrob. 2019 Sep 24;18(1):27. doi: 10.1186/s12941-019-0326-9.

Abstract

BACKGROUND

Identification of all possible HIV reservoirs is an important aspect in HIV eradication efforts. The urinary tract has however not been well studied as a potential HIV reservoir. In this pilot study we molecularly characterized HIV-1 viruses in urine and plasma samples to investigate HIV-1 replication, compartmentalization and persistence in the urinary tract.

METHODS

Prospectively collected urine and blood samples collected over 12-36 months from 20 HIV-1 infected individuals were analysed including sampling points from prior to and after ART initiation. HIV-1 pol gene RNA and DNA from urine supernatant and urine pellets respectively were analysed and compared to plasma RNA viruses from the same individual.

RESULTS

HIV-1 nucleic acid was detected in urine samples from at least one time point in 8/20 (40%) treatment-naïve subjects compared to 1/13 (7.7%) individuals on antiretroviral treatment (ART) during periods of plasma viral suppression and 1/7 (14.3%) individuals with virological failure. HIV-1 RNA was undetectable in urine samples after ART initiation but HIV-1 DNA was detectable in one patient more than 6 months after treatment initiation. There was co-clustering of urine-derived pol sequences but some urine-derived sequences were interspersed among the plasma-derived sequences.

CONCLUSIONS

Suppressive ART reduces HIV-1 replication in the urinary tract but HIV-1 DNA may persist in these cells despite treatment. A larger number of sequences would be required to confirm HIV compartmentalization in the urinary tract.

摘要

背景

鉴定所有可能的 HIV 储存库是 HIV 根除工作的一个重要方面。然而,尿路尚未被很好地研究作为潜在的 HIV 储存库。在这项初步研究中,我们通过分子方法对尿液和血浆样本中的 HIV-1 病毒进行了特征分析,以研究 HIV-1 在尿路中的复制、区室化和持久性。

方法

前瞻性收集了 20 名 HIV-1 感染者在 12-36 个月期间的尿液和血液样本,包括在开始 ART 之前和之后的采样点。分别分析了尿液上清液和尿液沉淀物中的 HIV-1 pol 基因 RNA 和 DNA,并与同一个体的血浆 RNA 病毒进行了比较。

结果

在未接受抗病毒治疗的 20 名受试者中,有 8/20(40%)至少有一个时间点的尿液样本中检测到 HIV-1 核酸,而在接受抗病毒治疗期间(ART)的 13 名受试者中,有 1/13(7.7%)在血浆病毒抑制时和 7 名有病毒学失败的受试者中,有 1/7(14.3%)在尿液样本中检测到 HIV-1 RNA。ART 后 HIV-1 RNA 在尿液样本中无法检测到,但在治疗开始后 6 个月以上的一名患者中仍可检测到 HIV-1 DNA。尿液衍生的 pol 序列存在共聚类,但一些尿液衍生的序列散布在血浆衍生的序列之间。

结论

抑制性 ART 可减少 HIV-1 在尿路中的复制,但尽管治疗,HIV-1 DNA 仍可能在这些细胞中持续存在。需要更多的序列来确认 HIV 在尿路中的区室化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9cc/6760049/0ae5a16c8a45/12941_2019_326_Fig1_HTML.jpg

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