REGULATION OF HIV-1 CORECEPTORS

HIV-1 辅助受体的调节

• 批准号: 6019921
• 负责人: HARIBABU BODDULURI
• 金额: $ 4.03万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6019921
• 关键词: HIV infections; Italy; cell line; chemokine; cytokine receptors; helper T lymphocyte; human immunodeficiency virus 1; mitogen activated protein kinase; phospholipase A2; receptor expression; receptor sensitivity; virus infection mechanism; virus receptors

The chemokines are a family of structurally related peptides that interact through cell surface G-protein coupled receptors in leukocytes to mediate diverse biological and biochemical activities such as adhesion, directed migration and activation. They play a major role in the pathophysiology of many inflammatory disorders. Chemokine receptors CCR5 or CXCR4 were identified as essential co-receptors for the entry of human immunodeficiency virus HIV-1 into CD4 positive cells. While CCR5 is the target for the entry of primary viruses CXCR4 may be important in the progression to AIDS from asymptomatic infection. The overall objective of the parent proposal is to delineate the pathways of CXCR4 signaling, desensitization and internalization using the RBL-2H3 cells stably co-expressing epitope-tagged native or mutated CXCR4 along with human CD4. In this AIDS-FIRCA, Dr. Sozzani proposes to utilize many reagents (epitope-tagged, green fluorescent protein tagged native and mutated CXCR4 DNAs and transfected RBL cell lines) developed for the parent proposal to determine the role of MAPKs on cPLA2 activation by the ligand SDF-1 and the relevance of this pathway to leukocyte chemotaxis using both pharmacological and biochemical approach. The ability of the HIV-1 envelope glycoproteins (gp120) to induce second messenger formation in CXCR4-expressing RBL-2H3 will be investigated. Activation of MAPKs, and cPLA2 will be evaluated and correlated with the ability of gp120 proteins to induce cell migration. The parent laboratory is utilizing and HIV-1 infection permissive human astroglioma cell line, U87, transfected with human CD4 and native or mutated CXCR4 to determine the role of the signaling evens and internalization in HiV-1 infection. The studies on cPLA2 and MAPKs in RBLs will provide a basis for extension of the same to human cell lines in the parent laboratory and to determine the role of these pathways in HIV-1 infection.

趋化因子是与结构相关的肽家族 通过白细胞中的细胞表面G蛋白偶联受体相互作用 介导多种生物学和生化活性，例如粘附， 定向迁移和激活。他们在 许多炎症性疾病的病理生理学。趋化因子受体CCR5或 CXCR4被确定为人类进入的必不可少的共受体 免疫缺陷病毒HIV-1进入CD4阳性细胞中。而CCR5是目标 对于主要病毒的进入，cxcr4可能在进展中很重要 无症状感染的艾滋病。父母建议的总体目标 是描绘CXCR4信号传导，脱敏和 使用RBL-2H3单元稳定地共表达表位标记的内在化 天然或突变的CXCR4以及人CD4。 在此艾滋病 - 菲尔卡（Aids-Firca）中，Sozzani博士建议利用许多试剂 （表位标签，绿色荧光蛋白标记为本机和突变的CXCR4 DNA 和转染的RBL细胞系）为父案提案开发以确定 MAPK在配体SDF-1激活CPLA2激活的作用以及 使用药理和生化的这种白细胞趋化性的途径 方法。 HIV-1信封糖蛋白（GP120）诱导的能力 将研究表达CXCR4的RBL-2H3中的第二信使形成。 将评估MAPK和CPLA2的激活 GP120蛋白诱导细胞迁移的能力。家长实验室是 利用和HIV-1感染允许的人类星形胶质瘤细胞系U87， 用人CD4和天然或突变的CXCR4转染，以确定 HIV-1感染中的信号传递和内在化。研究 RBL中的CPLA2和MAPKS将为人类扩展的基础 家长实验室中的细胞系并确定这些途径的作用 在HIV-1感染中。