Impairment of excitatory amino acid transport in astroglial cells infected with the human immunodeficiency virus type 1.
Impairment of excitatory amino acid transport in astroglial cells infected with the human immunodeficiency virus type 1.
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感染 1 型人类免疫缺陷病毒的星形胶质细胞中兴奋性氨基酸转运受损。
DOI：
10.1089/aid.1998.14.1329
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Kort,JJ
中科院分区：
文献类型：
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作者：
Kort,JJ
HIV-1 感染对星形胶质细胞功能的干扰可能导致艾滋病痴呆症 (ADC) 的发病机制。本研究调查了星形胶质细胞谷氨酸和天冬氨酸（哺乳动物中枢神经系统（CNS）中主要兴奋性氨基酸（EAA））的运输因HIV-1感染而改变的可能性。人类 U251 神经胶质瘤细胞被 HIV-1 的脑分离株 SF162 感染。 HIV-1 在神经胶质细胞中持续存在数月之久。这种神经胶质细胞的非生产性感染的特点是，Nef 在感染期间持续表达，并且结构病毒蛋白短暂存在，包括病毒跨膜糖蛋白 gp41（在 HIV-1 感染后最初 2 周内检测到）。急性HIV-1感染的神经胶质细胞中gp41的存在与ind-[3H]天冬氨酸摄取减少36%同时发生，这是由于福特天冬氨酸最大转运能力(vmax)的降低。 U251 神经胶质瘤细胞中典型星形细胞谷氨酸转运蛋白 EAAT1 和 EAAT2 的表达并未因 HIV-1 感染而改变。为了确定病毒蛋白 gp120、gp41 或 Nef 是否参与急性 HIV-1 感染的胶质细胞中 EAA 转运的损伤、慢病毒裂解肽 1 型 (LLP-1)（对应于 gp41 的羧基末端）、重组 SF2 gp120 和重组 LAI Nef ond-[3H]天冬氨酸摄取和 研究了神经胶质细胞中谷氨酸的释放。只有 LLP-1 减少了[3H]天冬氨酸的摄取，并以浓度依赖性方式促进神经胶质细胞释放谷氨酸。这些结果表明，gp41 的羧基末端会损害神经胶质细胞中的 EAA 转运，这可能会导致中枢神经系统 HIV-1 感染中神经元的兴奋性毒性损伤。
Perturbation of astrocyte functions by HIV-1 infection may contribute to the pathogenesis of AIDS dementia complex (ADC). The present study investigated the possibility that astroglial transport of glutamate and aspartate, the major excitatory amino acids (EAAs) in the mammalian central nervous system (CNS), is altered by HIV-1 infection. Human U251 glioma cells were infected with the brain isolate SF162 of HIV-1. HIV-1 persisted in glial cells over several months. This nonproductive infection of glial cells was characterized by persistent expression of Nef over the time of the infection, and the transient presence of structural viral proteins, including the viral transmembrane glycoprotein gp41, which was detected during the initial 2 weeks following HIV-1 infection. The presence of gp41 in acutely HIV-1-infected glial cells coincided with a 36% decrease ind-[3H]aspartate uptake, owing to a reduction in the maximal transport capacity (vmax) ford-aspartate. The expression of typical astrocytic glutamate transporters EAAT1 and EAAT2 in U251 glioma cells was not altered by HIV-1 infection. To determine whether viral protein gp120, gp41, or Nef was involved in the impairment of EAA transport in acutely HIV-1-infected glial cells, effects of lentiviral lytic peptide type 1 (LLP-1) (corresponding to the carboxy terminus of gp41), recombinant SF2 gp120, and recombinant LAI Nef ond-[3H]aspartate uptake and the release of glutamate in glial cells were investigated. Only LLP-1 reducedd-[3H]aspartate uptake and facilitated the release of glutamate from glial cells in a concentration-dependent manner. These results suggest that the carboxy terminus of gp41 impairs EAA transport in glial cells, which may contribute to excitotoxic damage to neurons in HIV-1 infection of the CNS.