STRUCTURE AND FUNCTION OF ALEUTIAN MINK DISEASE PARVOVIRUS (ADV) GENOME

阿留申水貂病细小病毒 (ADV) 基因组的结构和功能

• 批准号: 6288816
• 负责人: Marshall Elliott Bloom
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/6288816
• 关键词: Baculoviridae; Carnivora; Parvoviridae; X ray crystallography; capsid; computer assisted sequence analysis; cryoscopy; genome; host organism interaction; laboratory rabbit; microorganism culture; microorganism immunology; nucleic acid sequence; protein structure function; recombinant virus; virion; virulence; virus antigen; virus genetics

Persistent infection of mink with Aleutian mink disease parvovirus (ADV) leads to progressive immune disorder characterized by high levels of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. Virus is not neutralized in vivo and ADV exists in infectious immune complexes. Isolates of ADV differ markedly in their ability to induce AD; some like ADV-Utah and ADV-TR are highly pathogenic in vivo, but are replication defective for CRFK cells. The cell-culture ADV-G is replication competent for CRFK, but replicates poorly, if at all, in mink and does not cause progressive disease. A major goal of this project is to correlate specific DNA sequences of the ADV genome to functional correlates, such as pathogenicity determinants and strain variation. Another major goal is to study the actual structure of the ADV virion. Understanding of the structure at high resolution will enable us to (a) map epitopes and pathogenicity determinants to discreet coordinates on the viral particle, (b) relate structural features to the unique biology of ADV in vivo.In the past year, work on this project led to number of findings. A method was developed to purify ABP, the putative cellular receptor for ADV from CRFK cells; an antibody against ABP was developed. Initial attempts at N-terminal sequencing were unsuccessful, possibly due to a blocked N- terminus. By studying viruses chimeric between ADV-G and ADV-Utah, we identified capsid protein residues that regulate in vivo and in vitro replication. One chimeric virus, H534D, replicated in vivo and induced a novel hepatocellular lesion that resembled Reye?s syndrome. - Parvoviruses, Aleutian mink disease parvovirus, virus structure, viral pathogenesis, host range, virus receptors

水貂持续感染阿留申水貂病细小病毒（ADV）会导致进行性免疫紊乱，其特征是高水平的抗病毒抗体、高丙种球蛋白血症、浆细胞增多症和免疫复合物疾病。病毒在体内不会被中和，ADV 存在于传染性免疫复合物中。 ADV 分离株在诱发 AD 的能力上存在显着差异；有些如 ADV-Utah 和 ADV-TR 在体内具有高致病性，但对 CRFK 细胞有复制缺陷。细胞培养物 ADV-G 对 CRFK 具有复制能力，但在水貂中复制效果较差（如果有的话），并且不会引起进行性疾病。该项目的一个主要目标是将 ADV 基因组的特定 DNA 序列与功能相关物关联起来，例如致病性决定因素和毒株变异。另一个主要目标是研究 ADV 病毒粒子的实际结构。了解高分辨率的结构将使我们能够 (a) 将表位和致病性决定因素映射到病毒颗粒上的离散坐标，(b) 将结构特征与 ADV 体内的独特生物学联系起来。在过去的一年里，我们开展了这方面的工作项目得出了许多发现。开发了一种从 CRFK 细胞中纯化 ABP 的方法，ABP 是 ADV 的假定细胞受体；开发了针对 ABP 的抗体。最初的 N 端测序尝试未成功，可能是由于 N 端被阻断。通过研究 ADV-G 和 ADV-Utah 之间的嵌合病毒，我们鉴定了调节体内和体外复制的衣壳蛋白残基。一种嵌合病毒 H534D 在体内复制并诱导一种类似于雷耶氏综合征的新型肝细胞病变。 - 细小病毒、阿留申水貂病细小病毒、病毒结构、病毒发病机制、宿主范围、病毒受体