B19 PARVOVIRUS AND ADENO-ASSOCIATED VIRUS

B19 细小病毒和腺相关病毒

• 批准号: 3757656
• 负责人: N S YOUNG
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3757656
• 关键词: Parvoviridae; active immunization; adeno associated virus group; antiviral antibody; capsid; congenital hemolytic anemia; gene expression; gene therapy; genetic transduction; hematopoietic stem cells; hemoglobinurias; human genetic material tag; human subject; human tissue; immunohematology; laboratory rabbit; neutralizing antibody; pregnancy infection; synthetic vaccines; transfection /expression vector; viral vaccines; virus antigen; virus diseases; virus genetics; virus protein

Our laboratory performs basic and clinical studies of the B19 parvovirus, the only member of the Parvoviridae family pathogenic in humans. Acute infection causes fifth disease, ad childhood rash illness and a polyarthralgia syndrome in adults. In patients with underlying hemolysis, acute infection results in transient aplastic crisis. In patients with underlying immunodeficiency, virus infection persists and causes chronic anemia; parvovirus infection is a cause of anemia in patients with AIDS. The virus is tropic for erythroid progenitor cells due to its use os erythrocyte P antigen. during the past year, we have identified two new parvovirus diseases. In utero infection can result in congenital anemia. In some children, parvovirus infection can be followed by severe hemolytic anemia in a syndrome termed paroxysmal cold hemoglobinuria. In continuation of vaccine studies, we have demonstrated that synthetic peptides of 20 amino acids, derived from the unique region of the minor capsid protein, elicit neutralizing antibody responses in rabbits. The genetic regulation of B19 parvovirus has been elucidated by identification of functionally active YY1 binding sites in the terminal repeat and promoter regions. An efficient method of purification of YY1 in a baculovirus system has been developed. The cytotoxic effect of the nonstructural protein has been shown to depend on intact nucleotide triphosphate binding regions. We have expanded out parvovirus studies to include adeno-associated virus as a vector for gene therapy. We have demonstrated that adeno-associated virus can transduce a human globin gene into human hematopoietic progenitor cells with high efficiency, resulting in significant protein production. A method to study transient expression of adeno-associated virus in cells under non- selective conditions has been developed.

我们的实验室进行B19细小病毒的基础和临床研究， 细小病毒科中唯一对人类致病的病毒。 急性 感染导致第五种疾病，即儿童皮疹疾病和 成人多关节痛综合征。 在基础疾病患者中， 溶血、急性感染导致短暂性再生障碍危象。 在 存在潜在免疫缺陷的患者，病毒感染持续存在， 引起慢性贫血;细小病毒感染是贫血的原因， 艾滋病患者。 该病毒嗜红系祖细胞 因为它使用了红细胞P抗原。 在过去一年中， 发现了两种新的细小病毒病。 子宫内感染可能导致 先天性贫血 在某些儿童中，细小病毒感染可 随后出现严重的溶血性贫血，称为阵发性感冒 血红蛋白尿 在疫苗研究的继续中，我们已经证明 由20个氨基酸组成的合成肽， 的次要衣壳蛋白，引发中和抗体反应， 家兔 阐明了B19细小病毒的遗传调控 通过鉴定功能活性的YY 1结合位点， 末端重复序列和启动子区。 的有效方法 已经开发了在杆状病毒系统中纯化YY 1的方法。 的 非结构蛋白的细胞毒性作用已被证明依赖于 在完整的核苷酸三磷酸结合区域上。 我们已经扩展到 细小病毒研究包括腺相关病毒作为基因载体 疗法 我们已经证明腺相关病毒可以通过 将人珠蛋白基因导入人造血祖细胞， 效率，导致显著的蛋白质产量。 的方法 非体外培养条件下腺相关病毒在细胞中瞬时表达研究 选择性条件已经形成。