PATHOGENESIS OF ALEUTIAN DISEASE VIRUS INFECTION

本项目的范围是研究水貂感染 水貂阿留申病细小病毒（ADV）。 在过去的一年里，我们开发了 链特异性RNA杂交探针有助于定位病毒的位点 复制的 探测器的基本原理是基于这样一个事实， 病毒DNA（RF）的复制形式含有“+”和“-”义 单链，但单链病毒体DNA（SS DNA）大于 90%“-”有义;因此，有义探针“+”与SS DNA和 也与双链体RF反应，而“-”有义探针优先与 射频。 当用从感染了剧毒的水貂中提取的DNA进行测试时， ADV-Utah I株感染后10天， 肠系膜淋巴结（MLN）、肝脏、脾脏和肠道，但仅在肠道和 第43天的MLN。 在10、43和60天时，在这些组织中观察到SS DNA， 与受感染的容许细胞培养物相比， 比RF。 这些结果表明，在成年水貂中，ADV可能 在肠道和淋巴网状组织中复制。 我们还用了这些 探针，以调查最近描述的暴发性间质 ADV引起的新生水貂肺炎。 这种疾病是 其特征在于局限于肺部的大体病理学病变， 透明膜的发展和病毒包涵体的存在。 当组织学病变，核内包涵体的存在， 核内ADV抗原与病毒DNA水平相关 物种，得出的结论是，肺，可能是肺泡II型细胞， 是病毒复制和细胞病理学的主要目标， 套件 在MLN中也发现低水平的RF，表明ADV 在这个器官中也有重复，尽管没有明显的细胞病理学。 的 数据表明ADV在新生儿肺组织中的复制模式 类似于在允许的细胞培养中看到的，但是， 在其他试剂盒器官中的复制更接近于 描述成貂。

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 developed strand-specific RNA hybridization probes to help localize sites of viral replication. The rationale for the probes is based on the fact that replicative forms of viral DNA (RFs) contain both "+" and "-" sense strands, but that the single stranded virion DNA (SS DNA) is greater than 90% "-" sense; thus, probes "+" in sense react with both the SS DNA and also with the duplex RFs, while "-" sense probes react preferentially with RFs. When tested against DNA extracted from mink infected with virulent ADV-Utah I strain, RFs were detected at 10 days after infection in mesenteric lymph node (MLN), liver, spleen, and gut, but only in gut and MLN at 43 days. SS DNA was noted in these tissues at 10, 43, and 60 days, and in contrast to infected permissive cell cultures, was more abundant than the RFs. These findings suggested that in adult mink, ADV may replicate in gut as well as lymphoreticular tissues. We also used these probes to investigate the recently described fulminant interstitial pneumonitis caused by ADV in newborn mink kits. This disease is characterized by gross pathological lesions confined to the lungs, the development of hyaline membranes, and the presence of viral inclusions. When histological lesions, the presence of intranuclear inclusion bodies, and intranuclear ADV antigen were correlated with levels of viral DNA species, it was concluded that the lung, probably alveolar type-II cells, is the major primary target for viral replication and cytopathology in kits. RFs were also found in low level in MLN, suggesting that ADV replicates in this organ, too, although no cytopathology was evident. The data suggested that the pattern of ADV replication in newborn lung tissue is similar to that seen in permissive cell cultures, but that the replication in other kit organs more closely resembles the pattern described for adult mink.