ROLES(S) OF GLYCOSPHINGOLIPIDS IN NEURAL AIDS

鞘糖脂在神经艾滋病中的作用

• 批准号: 6146819
• 负责人: Cara-Lynne Schengrund
• 金额: $ 22.66万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6146819
• 关键词: AIDS /HIV neuropathy; HIV envelope protein gp120; brain cell; embryo /fetus tissue /cell culture; glycosphingolipids; human fetus tissue; human immunodeficiency virus 1; virus infection mechanism

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.

描述（改编自申请人的摘要）：糖鞘脂（GSL）具有 作为人类免疫缺陷病毒（HIV）的融合辅因子， 艾滋病的病原体。拟议研究的总体目标是 确定GSL在HIV-1相关gp 120与 中枢神经系统（CNS）的不同细胞类型或其模型，和 利用这些信息来开发这种相互作用的可能抑制剂。 重点放在CNS细胞或其可能的模型上，因为许多 感染HIV-1的个体最终会发展为HIV-1相关性痴呆 (HAD)在没有机会性感染的情况下。具体目标是 建议是：1）确定哪些GSL是 HIV-1相关gp 120。将进行实验以确认GSL是 HIV-1进入所必需的，在这些情况下， 将识别HIV-1粘附的GSL。2)决定...的贡献 GSL糖和神经酰胺部分与HIV-1相关的 gp120。将进行实验以确定糖是否 HIV-1粘附的每个GSL的一部分可以抑制HIV-1粘附到GSL 固定在塑料上，或者是“多价”糖或神经酰胺， 部分本身是需要的。3)确定HIV-1抑制剂是否 相关的gp 120介导的对GSL的粘附能够抑制gp 120介导的 病毒进入表达GSL的细胞。的有效性 将监测第二阶段确定的旨在阻断感染的抑制剂 使用小胶质细胞和星形细胞。病毒在诱导 在存在和不存在抑制剂的情况下，神经母细胞瘤细胞的凋亡将 也要确定。结果应表明GSL的部分 被HIV-1识别。它们还可以为制定一项 能够阻断HIV-1与其GSL融合辅因子粘附抑制剂， 阻止它进入细胞。