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

阿留申貂皮病细节病毒（ADV）对貂皮的持续感染导致进行性免疫疾病，其特征是高水平的抗病毒药抗体，高γ-球胶质素血症，浆细胞增多症和免疫复杂疾病。病毒不会在体内中和，并且在传染性免疫复合物中存在ADV。 ADV的分离株在诱导AD的能力方面明显不同。有些像adv-utah和adv-tr在体内具有高度致病性，但对于CRFK细胞而言，复制有缺陷。细胞培养ADV-G是CRFK胜任的复制，但在Mink中复制不佳（如果有的话），并且不会引起进行性疾病。该项目的主要目标是将ADV基因组的特定DNA序列与功能相关性相关联，例如致病性决定因素和应变变异。另一个主要目标是研究Adv Virion的实际结构。了解高分辨率下的结构将使我们能够（a）映射表位和致病性决定因素，以划分病毒粒子上的坐标，（b）将结构特征与vivo的独特生物学相关联。在过去的一年中，在该项目上发挥了许多发现。开发了一种方法来纯化ABP，这是CRFK细胞中ADV的推定细胞受体。开发了针对ABP的抗体。 N末端测序的初始尝试不成功，这可能是由于n-末端阻塞。通过研究Adv-G和Adv-Itah之间的嵌合病毒，我们确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，并诱导了一种类似于雷耶综合征的新型肝细胞病变。 - 细小病毒，阿留申貂皮病细节病毒，病毒结构，病毒发病机理，宿主范围，病毒受体