VIRUSES AND HEMATOPOEIESIS

病毒和造血作用

• 批准号: 6162707
• 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/6162707
• 关键词: AIDS vaccines; Parvoviridae; adeno associated virus group; capsid; clinical research; clinical trial phase I; drug design /synthesis /production; gene expression; gene therapy; genetic transduction; hematopoiesis; human immunodeficiency virus 1; human subject; human therapy evaluation; immunohematology; receptor binding; tissue /cell culture; transfection /expression vector; vaccine development; vector vaccine; viral vaccines; virus genetics; virus integration; virus protein; virus receptors

Studies of the interaction of hematopoietic cells and viruses have concentrated on interesting members of the Parvoviridae and Flaviviridae families. B19 parvovirus infects erythroid progenitor cells and infection in humans causes both the hematologic syndromes transient aplastic crisis and pure red cell aplasia as well as the common childhood exanthem fifth disease. Provoked by reports that B19 parvovirus might be involved in the etiology of acute and fulminant hepatitis syndromes, we have analyzed using the polymerase chain reaction a large number of liver samples: in our experience, approximately 30% of liver tissue contain detectable B19 parvovirus, regardless of the primary diagnosis. These results suggest that the virus may persist in small amounts in visceral tissue without medical consequence. We have also discovered and characterized another member of the Erythrovirus genus that infects pig-tailed macaque monkeys. This and other Erythroviruses share genetic homology and functional characteristics with B19 parvovirus. One member of the genus, simian parvovirus, may offer an animal model for human disease, as hydrops fatalis has been reproduced by experimental uterine inoculation during the mid-trimester of pregnancy. In vaccine trials, rhesus monkeys have been immunized with empty B19 parvovirus capsids that were formulated with several experimental adjuvants in order to elicit high titers of neutralizing antibodies. One such formulation should prove appropriate for a human vaccine to prevent parvovirus disease. Other viral studies include cloning and sequencing of a member of the adeno-associated virus genus (AAV), the tissue tropism of which differs from the conventional AAV-2; further experiments to determine the nature of the cell surface receptor for AAV-2; and functional analysis of the non-structural protein of B19 parvovirus, which is responsible for viral cell killing. Of the Flaviviridae, hepatitis G or GBV-C, a novel member of the flavi-pestivirus group, has been detected by gene amplification in a large number of normal individuals: approximately 6% of normal Vietnamese are viremic and more recent studies of children in the Washington area show that 9% of plasma samples contain GBV-C sequences. Genetic heterogeneity is high among all isolates sequenced to date. Whether GBV-C represents a true hepatitis virus, its tissue tropism, the nature of replication in the absence of a core protein, and the relationship of viral infection to disease remain important current questions.

造血细胞和病毒相互作用的研究 专注于细小病毒科和黄病毒科的有趣成员 家庭 B19细小病毒感染红系祖细胞， 人类感染引起短暂的血液学综合征 再生障碍性贫血危象和纯红细胞再生障碍性贫血以及常见的 儿童疹第五病。 据报道，B19 细小病毒可能参与了急性和暴发性的病因 肝炎综合征，我们分析了使用聚合酶链 大量肝脏样本的反应：根据我们的经验， 大约30%的肝组织含有可检测的B19细小病毒， 不管最初的诊断是什么 这些结果表明 病毒可以在没有医疗的情况下在内脏组织中少量存在 后果 我们还发现了另一个成员 感染长尾猕猴的红细胞病毒属。 这 和其他红细胞病毒共享遗传同源性和功能 具有B19细小病毒的特征。 猿属的一员，猿猴 细小病毒，可以提供一个人类疾病的动物模型，如水肿 致命的是通过实验性的子宫接种， 怀孕中期 在疫苗试验中， 用配制的空B19细小病毒衣壳免疫 与几种实验佐剂，以引起高滴度的 中和抗体 其中一种提法应证明是适当的 用于预防细小病毒病的人类疫苗。 其他病毒研究 包括腺相关病毒成员的克隆和测序 属（AAV），其组织向性不同于常规的 AAV-2;确定细胞表面性质的进一步实验 AAV-2的非结构性受体的功能分析 B19细小病毒的蛋白质，负责病毒细胞杀伤。 在黄病毒科、庚型肝炎病毒或GBV-C中， 黄瘟病毒组，已通过基因扩增检测到在一个 大量正常个体：约6%正常 越南人有病毒血症，最近对越南儿童的研究表明， 华盛顿地区的研究表明，9%的血浆样品含有GBV-C序列。 迄今为止测序的所有分离株的遗传异质性很高。 GBV-C是否代表真正的肝炎病毒，其组织嗜性， 在没有核心蛋白的情况下复制的性质， 病毒感染与疾病的关系仍然是当前重要的研究课题 问题.