PAROVIRUS (HUMAN) B19

细小病毒（人）B19

• 批准号: 3858051
• 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/3858051
• 关键词: Parvoviridae; aplastic anemia; cell biology; chronic disease /disorder; communicable disease diagnosis; communicable disease transmission; erythroid stem cell; human tissue; immunoglobulins; immunohematology; insect virus; ligase; virus cytopathogenic effect; virus diseases; virus protein

Our laboratory performs basic and clinical studies of the B19 parvovirus, the only member of parvoviradae family pathogenic in humans. Acute infection causes fifth disease, a 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 trophic for erythroid progenitor cells. We have made progress in B19 parvovirus biology in a number of areas over the last year. We have discovered the first case of congenital B19 parvovirus infection: transmission of the virus to the fetus resulted in chronic anemia at birth and death at 7 months; virus was restricted to the marrow and did not circulate. The recovery of an adult patient with congenital pure red cell aplasia, whose bone marrow showed B19 parvovirus, suggests that interleukin-3 may induce antibody formation to this virus, possibly of use in patients with AIDS-associated infection. We have induced neutralizing antibodies to B19 parvovirus using baculovirus-generated empty capsids in animals. This empty capsid system can be manipulated to increase the proportion of the minor capsid protein the minor capsid protein antigen contains a neutralizing epitope Because it is not required for virus assembly, substitution of heterologous proteins sequences in the unique region of the minor capsid antigen make empty parvovirus capsids useful as vaccine agents and for specific delivery of proteins. we have achieved propagation of B19 parvovirus outside of bone marrow using a megakaryocyte cell line derived from a patient with leukemia. The trophism of parvovirus for erythroid cells has been investigated at the molecular level. Based on the pattern of RNA transcription in cells transfected with parvovirus sequences, the function of the p(6) promotor in nonpermissive cells, and deletion mutations analyzed by RNA protection, we have concluded that a block in transcription in the middle of the genome exists in nonpermissive cells, possibly at an attenuator region downstream from the nonfunctional P44 promoter.

我们的实验室进行B19细小病毒的基础和临床研究， 是细小病毒科中唯一对人类致病的成员。 急性 感染导致第五种疾病，一种儿童皮疹疾病和一种 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。 该病毒对红系祖细胞有营养作用。 我们在B19细小病毒生物学的多个领域取得了进展， 最后一年 我们发现了第一例先天性B19 细小病毒感染：病毒传播给胎儿， 出生时慢性贫血，7个月时死亡;病毒仅限于 骨髓没有循环。 一个成年病人的康复 先天性纯红细胞再生障碍性贫血骨髓B19 细小病毒，表明白细胞介素-3可能诱导抗体形成， 这种病毒，可能用于艾滋病相关感染的患者。 我们已经诱导了B19细小病毒的中和抗体， 杆状病毒在动物体内产生的空衣壳。 这个空衣壳系统 可以被操纵以增加次要衣壳蛋白的比例 次要衣壳蛋白抗原含有中和表位， 对于病毒组装、异源的置换和非同源的重组， 次要衣壳抗原的独特区域中的蛋白质序列使得 空细小病毒衣壳可用作疫苗剂和用于特异性 蛋白质的递送。我们已经实现了B19细小病毒的增殖 骨髓外的巨核细胞系， 白血病患者。 细小病毒对红系细胞的营养作用 已经在分子水平上进行了研究。 根据 在用细小病毒序列转染的细胞中， p（6）启动子在非允许细胞中的功能，以及缺失 通过RNA保护分析突变，我们得出结论， 基因组中间的转录存在于非允许细胞中， 可能在非功能性P44下游的衰减器区域 启动子