PATHOGENESIS OF ALEUTIAN DISEASE VIRUS INFECTION

这个项目的范围是关于水貂感染的研究。 水貂细小病毒阿留申病(ADV)。在过去的一年 我们已经开始利用链-ADV感染的分析- 特异性原位分子杂交。其理论基础是 复制形式的Adv DNA(RFs)含有“+” 感觉核酸链，而病毒DNA主要是“-”在 有道理。因此，意义上为“-”的探测器将优先定义 复制位置，而“+”正义探针将另外 勾勒出隔离病毒的地点。我们已经申请了 这些探针在ADV感染中的应用 新生水貂组织培养细胞的体外培养和切片观察 ADV间质性肺炎。在体外始终允许的 感染后，双链RFs定位于细胞核。病毒粒子 DNA和衣壳蛋白存在于早期的细胞核中。 感染，但后来被转移到细胞质。这个 放射自显影颗粒清楚地定位在受感染的人身上 细胞，ADV抗原阳性细胞数为 与病毒DNA阳性的情况相同，这表明在这种情况下 允许系统中，所有含有病毒DNA的细胞也表达 病毒蛋白。在感染ADV的新生水貂中，细胞复制 ADV主要见于肺部。RFS和ADV抗原 主要在产生表面活性物质的肺泡中发现 II型细胞，其模式与观察到的 组织培养细胞。这一观察表明，新生儿 肺炎是由ADV引起的直接细胞病变引起的。 II型细胞，随后肺功能衰竭 表面活性剂。在其他器官中也发现了病毒DNA，但 链特异性探针使我们有可能显示大多数这种情况 DNA代表被隔离在吞噬细胞中的病毒 淋巴网状系统的元素。病毒粒子DNA，Adv 在正常组织中发现抗原和水貂免疫球蛋白。 这些感染的新生儿的肾小球，提示早期形式的 免疫复合体肾炎，完整的病毒粒子参与其中。

The scope of this project is the study of infections of mink with the Aleutian disease of mink parvovirus (ADV). In the past year we have begun the analysis of ADV infections utilizing strand- specific in situ molecular hybridization. The rationale is based on the fact that replicative forms of ADV DNA (RFs) contain "+" sense nucleic acid strands, whereas virion DNA is largely "-" in sense. Thus, probes that are "-" in sense will preferentially define sites of replication, whereas "+" sense probes will in addition delineate sites where virus is being sequestered. We have applied these probes in in situ hybridization to date on ADV infected tissue culture cells in vitro and on sections of newborn mink with ADV interstitial pneumonitis. Throughout permissive in vitro infection, duplex RFs were localized to the cell nuclei. Virion DNA and capsid proteins were found in the nuclei early in infection, but were later translocated to the cytoplasm. The autoradiographic grains were clearly localized over the infected cells, and the number of cells positive for ADV antigen was the same as that positive for viral DNA, suggesting that in this permissive system, all cells containing viral DNA also expressed viral proteins. In ADV infected neonatal mink, cells replicating ADV were found primarily in the lung. RFs and ADV antigens were found predominantly in the surfactant producing alveolar type II cells, and the pattern was similar to that observed for the tissue culture cells. This observation suggested that the neonatal pneumonitis results from a direct cytopathic infection by ADV of the type II cells, with subsequent depletion of pulmonary surfactant. Viral DNA was also found in other organs, but the strand specific probes made it possible to show that most of this DNA represented virus that was being sequestered in phagocytic elements of the lymphoreticular system. Virion DNA, ADV antigen and mink IgG were found in the histologically normal glomeruli of these infected neonates, suggesting an early form of immune complex nephritis in which intact virions participated.