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HIV-1启动子单核苷酸多态性与临床疾病严重程度相关。

HIV-1 Promoter Single Nucleotide Polymorphisms Are Associated with Clinical Disease Severity.

作者信息

Nonnemacher Michael R, Pirrone Vanessa, Feng Rui, Moldover Brian, Passic Shendra, Aiamkitsumrit Benjamas, Dampier Will, Wojno Adam, Kilareski Evelyn, Blakey Brandon, Ku Tse-Sheun Jade, Shah Sonia, Sullivan Neil T, Jacobson Jeffrey M, Wigdahl Brian

机构信息

Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.

Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.

出版信息

PLoS One. 2016 Apr 21;11(4):e0150835. doi: 10.1371/journal.pone.0150835. eCollection 2016.

DOI:10.1371/journal.pone.0150835
PMID:27100290
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4839606/
Abstract

The large majority of human immunodeficiency virus type 1 (HIV-1) markers of disease progression/severity previously identified have been associated with alterations in host genetic and immune responses, with few studies focused on viral genetic markers correlate with changes in disease severity. This study presents a cross-sectional/longitudinal study of HIV-1 single nucleotide polymorphisms (SNPs) contained within the viral promoter or long terminal repeat (LTR) in patients within the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. HIV-1 LTR SNPs were found to associate with the classical clinical disease parameters CD4+ T-cell count and log viral load. They were found in both defined and undefined transcription factor binding sites of the LTR. A novel SNP identified at position 108 in a known COUP (chicken ovalbumin upstream promoter)/AP1 transcription factor binding site was significantly correlated with binding phenotypes that are potentially the underlying cause of the associated clinical outcome (increase in viral load and decrease in CD4+ T-cell count).

摘要

先前确定的绝大多数1型人类免疫缺陷病毒（HIV-1）疾病进展/严重程度标志物都与宿主遗传和免疫反应的改变有关，很少有研究关注与疾病严重程度变化相关的病毒遗传标志物。本研究对德雷塞尔医学中心中枢神经系统艾滋病研究与根除研究（CARES）队列中的患者，进行了一项关于病毒启动子或长末端重复序列（LTR）中所含HIV-1单核苷酸多态性（SNP）的横断面/纵向研究。发现HIV-1 LTR SNP与经典临床疾病参数CD4+ T细胞计数和病毒载量对数相关。它们存在于LTR的已定义和未定义转录因子结合位点中。在已知的COUP（鸡卵清蛋白上游启动子）/AP1转录因子结合位点第108位鉴定出的一个新SNP，与可能是相关临床结果（病毒载量增加和CD4+ T细胞计数减少）潜在根本原因的结合表型显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/3c1f1a955b75/pone.0150835.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/a9278c90c521/pone.0150835.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/f19f44e1fb89/pone.0150835.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/5ce41666ba38/pone.0150835.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/9ec9bf1b2ddd/pone.0150835.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/3c1f1a955b75/pone.0150835.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/a9278c90c521/pone.0150835.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/f19f44e1fb89/pone.0150835.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/5ce41666ba38/pone.0150835.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/9ec9bf1b2ddd/pone.0150835.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/4839606/3c1f1a955b75/pone.0150835.g005.jpg

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