AIDS-DEMENTIA DUE TO GP120 HOMOLOGY TO NEUROLEUKIN

神经白细胞介素是一种多肽因子， 神经营养和淋巴因子活性。 GP 120的一个区域 HIV的外膜蛋白与 神经白细胞素 与ENV基因的一段同源 在所有HIV分离株中都是保守的 已报告信息。 重组神经白细胞介素载体 脊髓和感觉神经元在培养中的持续存活。 信息编码神经白细胞介素在大脑中表达， 假设神经白细胞介素对生长和 中枢神经系统内神经元的功能。 神经白介素也是一种 淋巴因子 它是一种凝集素刺激的T细胞产物， 体外培养人外周血淋巴细胞诱导免疫球蛋白合成 血单核细胞 我们假设这个序列 GP 120与神经白细胞介素的同源性有助于亚急性 脑炎和多克隆B细胞活化中看到的艾滋病。 我们的初步实验表明，GP 120蛋白具有 神经白细胞介素激动剂/拮抗剂活性， 存在于神经白细胞介素同源片段中。 表示我们 工作，我们建议确定是否GP 120的片段， 含有神经白细胞介素同源片段的脑炎 动物 我们还将证明， GP 120片段是由于神经白细胞介素依赖性机制， 并且该机制涉及激动剂/拮抗剂相互作用 与神经元上的神经白细胞素受体结合。 该项目可能导致 涉及治疗剂和/或肽疫苗的开发 对抗艾滋病病毒。

Neuroleukin is a polypeptide factor which exhibits both neurotrophic and lymphokine activities. A region of the GP120 external envelope protein of HIV is partially homologous to neuroleukin. The homology is to a segment of the ENV gene which is conserved in all HIV isolates for which sequence information has been reported. Recombinant neuroleukin supports the continued survival in culture of spinal and sensory neurons. Message encoding neuroleukin is expressed in brain and we hypothesize that neuroleukin is important for the growth and function of neurons within the CNS. Neuroleukin is also a lymphokine. It is a lectin-stimulated T-cell product and acts to induce immunoglobulin synthesis by cultured human peripheral blood mononuclear cells. We hypothesize that the sequence homology of GP120 to neuroleukin contributes to the subacute encephalitis and to the polyclonal B-cell activation seen in AIDs. Our initial experiments indicate that the GP120 protein has neuroleukin-agonist/antagonist activity and that the activity resides in the neuroleukin-homology segment. To extend our work, we propose to determine if fragments of GP120 which contain the neuroleukin homology segment are encephalitic in animals. We also will show that the pathological effects of GP120 fragments are due to a neuroleukin-dependent mechanism, and that that mechanism involves agonist/antagonist interaction with the neuroleukin receptor on neurons. The project could lead to development of a therapeutic agent and/or a peptide vaccine against HIV.