ROLES(S) OF GLYCOSPHINGOLIPIDS IN NEURAL AIDS

描述(改编自申请人的摘要)：甘氨酸磷脂(GSLS)有 被认为是人类免疫缺陷病毒(HIV)的融合辅助因子 艾滋病的病原体。拟议研究的总体目标是 确定GSLS在HIV-1相关gp120与GSLS相互作用中的作用(S) 中枢神经系统(CNS)的不同细胞类型或其模型，以及 利用这些信息来开发可能的抑制这种相互作用的药物。 重点放在中枢神经系统细胞或其可能的模型上，因为许多 感染HIV-1的人最终会患上HIV-1相关性痴呆症 (HAD)在没有机会感染的情况下。这样做的具体目的是 建议是：1)确定哪个GSL(S)是(S)的配体 HIV-1相关的gp120。将进行实验以确认GSLS是 对于进入HIV-1是必要的，在必要的情况下， 将确定HIV-1坚持的GSLS。2)确定以下项目的贡献 GSL糖和神经酰胺部分与HIV-1相关的相互作用 Gp120。将进行实验以确定糖类是否 HIV-1所附着的GSL的一部分可以抑制HIV-1与GSL的黏附 固定在塑料上，或者是“多价”糖或神经酰胺 这一部分本身是需要的。3)确定HIV-1的抑制剂是否 相关的gp120介导的对GSL的黏附能够抑制gp120介导的 病毒进入表达GSL的细胞。这项计划的成效 将监测在第二个目标中确定的用于阻断感染的抑制剂 使用小胶质细胞和无核细胞。病毒在诱导性方面的有效性 Will抑制剂存在和不存在时神经母细胞瘤细胞的凋亡 也被确定了。结果应该表明GSL的部分(S) 被HIV-1识别。它们还可以为开发一个 从而能够阻断HIV-1与其GSL融合辅助因子黏附的抑制剂 阻止它进入细胞。

Description (Adapted from Applicant's abstract): Glycospingolipids (GSLs) have been implicated as fusion co-factors for human immunodeficiency virus (HIV) the causative agent of AIDS. The overall goal of the proposed research is to determine the role(s) of GSLs in the interaction of HIV-1-associated gp120 with different cell types of the central nervous system (CNS) or models thereof, and to use that information to develop possible inhibitors of that interaction. Emphasis is placed on CNS cells or possible models thereof because many individuals infected with HIV-1 eventually develop HIV-1-associated dementia (HAD) in the absence of opportunistic infection. The specific aims of this proposal are to: 1) identify which GSL(s) is/are the ligand(s) for HIV-1-associated gp120. Experiments will be done to confirm that GSLs are necessary for HIV-1 entry and, in those instances where they are necessary, the GSLs adhered to by HIV-1 will be identified. 2) determine the contribution of the GSL saccharide and ceramide moieties to interactions with HIV-1-associated gp120. Experiments will be carried out to determine whether the saccharide portion of each GSL adhered to by HIV-1 can inhibit HIV-1 adherence to the GSL immobilized on plastic or whether a "multivalent" saccharide or the ceramide portion per se is needed. 3) determine whether the inhibitor of HIV-1 associated gp120-mediated adherence to a GSL is able to inhibit gp120-mediated entry of the virus into cells expressing the GSL. The effectiveness of the inhibitor identified in the 2nd aim at blocking infection will be monitored using microglia and asrtrocytes. The effectiveness of the virus at inducing apoptosis in neuroblastoma cells in the presence and absence of inhibitor will also be ascertained. The results should indicate the portion of the GSL(s) recognized by HIV-1. They may also provide the basis for development of an inhibitor able to block adherence of HIV-1 to its GSL fusion co-factor thereby blocking its entry into the cell.