Alvarez Susana, Jiménez José Luis, Serramía M Jesús, González Milagros, Cantó-Nogués Carmen, Muñoz-Fernández M Angeles
Molecular Immunobiology Laboratory, Gregorio Marañón University General Hospital, 28807 Madrid, Spain.
J Mol Neurosci. 2006;29(2):131-44. doi: 10.1385/JMN:29:2:131.
Despite HAART, a significant number of HIV-1-infected patients develop neurological complications. However, the presence of specific neurotropic HIV-1 strains, the extent of viral replication in the brain, and the type of cells infected remain controversial issues. To address this controversy we have analyzed different V3 loop sequences of viral isolates from four vertically HIV-1-infected children who developed HIV-1-related encephalopathy. Moreover, we have determined that some biological and molecular properties of HIV-1 might contribute to AIDS neurological dysfunctions. We detected very different HIV-1 isolates (X4 and R5) in the brain despite no great differences in clinical, pathological, or immunological parameters. In vitro, no differences in replicative competence in glial or neuroblastoma cells were observed between virus isolated from the blood of children with or without clinical neurological symptoms. The expression of both CXCR4 and CCR5 RNAs was observed in the brain independently of HIV-1 infection and viral strain predominant in this location. Our results failed to show a particular phenotypic property of the HIV-1 virus that might explain its neurovirulence and/or neurotropism.
尽管有高效抗逆转录病毒治疗(HAART),仍有相当数量的HIV-1感染患者出现神经并发症。然而,特定嗜神经HIV-1毒株的存在、病毒在脑内的复制程度以及被感染细胞的类型仍是存在争议的问题。为解决这一争议,我们分析了4名患HIV-1相关脑病的垂直感染HIV-1儿童的病毒分离株的不同V3环序列。此外,我们已确定HIV-1的某些生物学和分子特性可能导致艾滋病神经功能障碍。尽管在临床、病理或免疫参数方面没有很大差异,但我们在脑中检测到了非常不同的HIV-1分离株(X4和R5)。在体外,从有或无临床神经症状的儿童血液中分离出的病毒在神经胶质细胞或神经母细胞瘤细胞中的复制能力没有差异。在脑中观察到CXCR4和CCR5 RNA的表达,与HIV-1感染及该部位占主导的病毒株无关。我们的结果未能显示出HIV-1病毒可能解释其神经毒性和/或嗜神经特性的特定表型特征。