BIOLOGY OF LENTIVIRUS SURFACE CARBOHYDRATES

慢病毒表面碳水化合物的生物学

• 批准号: 3139368
• 负责人: OPENDRA NARAYAN
• 金额: $ 16.2万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-15 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3139368
• 关键词: O glycosidase; Retroviridae; antibody neutralization test; antibody specificity; antiserum; antiviral antibody; carbohydrate structure; carbohydrates; cell fusion; chemical binding; exoenzyme; glycopeptides; glycosyltransferase; human immunodeficiency virus 1; immune complex; macrophage; oligosaccharides; peptidases; phagocytosis; radiotracer; receptor mediated endocytosis; sialate; tissue /cell culture; virus antigen; virus envelope; virus infection mechanism; virus morphology; virus replication

HIV and the animal lentiviruses are poor inducers of neutralizing antibodies either during infection or in immunized experimental animals. Further, the effectiveness of neutralizing antibodies in protecting against HIV Infection is difficult to evaluate because of lack of data on differences between the affinity of antibodies for the virus and virus for the host cell. Studies on neutralization of the animal lentiviruses show that affinity between antibodies and virus is very low. Morevoer, viruses which are the poorest inducers of, and reactors with, neutralizing antobides are covered with a dense layer of carbohydrates. Our hypothesis is that viral surface carbohydrates are crucial for inducing and reacting with neutralizing antibodies and for binding to cells. Preliminary data already show that neuraminidase has major biological effects on the viruses. Using various substrates of virus, virus-infected cells and deglycosylated virus-infected cells to absorb immune sera; we will determine whether virus surface carbohydrates are the major epitopes in virus neutralization. We will also determine whether the viral carbohydrates are essential for binding of the virus to cells and later penetration of the cells. Finally, we will perform a detailed analysis of the structure of the viral carbohydrates with respect to O- and N-linked glycosylation on two prototype viruses that vary widely in biological properties.

HIV和动物慢病毒是中和的不良诱导剂 在感染期间或免疫实验中的抗体 动物 此外，中和抗体在抗肿瘤治疗中的有效性也是显而易见的。 预防艾滋病毒感染很难评估，因为 缺乏抗体亲和力差异的数据， 病毒和病毒的宿主细胞。 中和研究 的动物慢病毒显示抗体之间的亲和力 病毒含量很低。 更重要的是， 包括中和氧化物的诱导剂和反应器 有一层厚厚的碳水化合物 我们的假设是病毒 表面碳水化合物是诱导和反应的关键， 中和抗体和结合细胞。 初步数据 已经表明神经氨酸酶对 病毒 利用病毒的各种底物， 和去糖基化的病毒感染细胞吸收免疫血清;我们 将决定病毒表面的碳水化合物是否是 表位在病毒中和中的作用。 我们还将确定 病毒的碳水化合物对于病毒与 细胞和随后的细胞渗透。 最后，我们将执行一个 病毒碳水化合物结构的详细分析， 关于两种原型病毒上的O-和N-连接糖基化 在生物学特性上差异很大。