Shiramizu Bruce, Lau Emily, Tamamoto Alyson, Uniatowski Justin, Troelstrup David
Hawaii AIDS Clinical Research Program, University of Hawaii, Honolulu, HI.
J Investig Med. 2006 Dec;54(8):468-72. doi: 10.2310/6650.2006.06007.
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.
该研究的目的是评估在小儿脑脊液(CSF)中检测人类免疫缺陷病毒1型(HIV-1)前病毒脱氧核糖核酸(DNA)以及单核细胞趋化蛋白1(MCP1)相关单核苷酸多态性(SNP)的可行性。HIV DNA和MCP1 SNP的重要性已被认为在成人获得性免疫缺陷综合征(AIDS)进展和神经认知障碍中具有独立的重要意义。在儿童中,检测脑脊液中的这两个因素可能有助于我们了解导致HIV-1相关脑病(HAE)的神经致病过程。通过实时聚合酶链反应对27例围生期感染HIV-1且患有HAE的儿童的储存标本进行HIV DNA拷贝数检测,并与通过消化扩增的361 bp片段测量的MCP1 2578G SNP突变进行比较。与MCP1 2578G SNP相比,与野生型相比,有大量携带该突变的儿童HIV DNA水平较高(p < 0.01),在HIV-1血清阴性对照标本中未检测到相关水平。有6份脑脊液标本有足够的上清液通过酶联免疫吸附测定法测量MCP1水平,结果显示携带MCP1 2578G突变的儿童MCP1水平较高。本研究首次证明,可以检测脑脊液中的HIV DNA和MCP1 SNP,它们可能成为未来临床研究中了解小儿HAE发病机制的潜在工具。