Feasibility Assessment of Cerebrospinal Fluid from HIV-1-Infected Children for HIV Proviral DNA and Monocyte Chemoattractant Protein 1 Alleles

Feasibility Assessment of Cerebrospinal Fluid from HIV-1-Infected Children for HIV Proviral DNA and Monocyte Chemoattractant Protein 1 Alleles
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DOI:
10.2310/6650.2006.06007
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发表时间:
2006-12
影响因子:
2.6
通讯作者:
B. Shiramizu;E. Lau;A. Tamamoto;J. Uniatowski;D. Troelstrup
B. Shiramizu;E. Lau;A. Tamamoto;J. Uniatowski;D. Troelstrup
中科院分区:
医学4区
文献类型:
--
作者:
B. Shiramizu;E. Lau;A. Tamamoto;J. Uniatowski;D. Troelstrup

文献摘要

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本研究的目的是评估测量儿童脑脊液(CSF)中人类免疫缺陷病毒1(HIV-1)前病毒脱氧核糖核酸(DNA)和单核细胞趋化蛋白1(MCP 1)相关单核苷酸多态性(SNP)的可行性。HIV DNA和MCP 1 SNP的重要性已被认为在成人获得性免疫缺陷综合征(AIDS)和神经认知障碍的进展中是独立重要的。在儿童中,测量CSF中的这两种因素可能有助于我们了解导致HIV-1相关脑病(HAE)的神经病理过程。通过实时聚合酶链反应对27例围产期HIV-1感染HAE儿童的储存库标本进行HIV DNA拷贝评估,并与通过消化扩增的361 bp片段测量的MCP 1 2578 G SNP突变进行比较。当与MCP 1 2578 G SNP相比时,与野生型相比,具有突变的显著数量具有高HIV DNA(p <0.01),在HIV-1血清阴性对照标本中未检测到水平。有6份CSF样本的上清液足以通过酶联免疫吸附试验测定MCP 1水平,结果显示MCP 1 2578 G突变的样本中MCP 1水平较高。这项研究首次表明,CSF HIV DNA和MCP 1 SNP可以测量,并可能成为未来临床研究的潜在工具,以了解儿科HAE的发病机制。
The objective of the study was to assess the feasibility of measuring human immunodeficiency virus 1 (HIV-1) proviral deoxyribonucleic acid (DNA) and associated single-nucleotide polymorphism (SNP) of monocyte chemoattractant protein 1 (MCP1) in pediatric cerebrospinal fluid (CSF). The importance of HIV DNA and MCP1 SNP has been suggested to be independently important in progression to acquired immune deficiency syndrome (AIDS) and neurocognitive impairment in adults. In children, measuring both factors in the CSF may help us understand the neuropathogenic process leading to HIV-1-associated encephalopathy (HAE). Repository specimens from 27 perinatally HIV-1-infected children with HAE were assessed for HIV DNA copy by real-time polymerase chain reaction and compared with MCP1 2578G SNP mutations measured by digesting amplified 361 bp fragments. When compared with MCP1 2578G SNP, a significant number with the mutation had high HIV DNA compared with those with wild type (p < .01), with no levels detected in HIV-1-seronegative control specimens. There were six CSF specimens with enough supernatant to measure MCP1 levels by enzyme-linked immunosorbent assay, which showed high levels in those with the MCP1 2578G mutation. This study demonstrates, for the first time, that CSF HIV DNA and MCP1 SNP can be measured and could be potential tools in future clinical studies to understand the pathogenesis of pediatric HAE.