PATHOGENESIS OF ALEUTIAN DISEASE VIRUS INFECTION

这个项目的范围是关于水貂感染的研究。 阿留申水貂病细小病毒(ADV)。在过去的一年里我们 已经扩展了链特异性原位分子的使用 用杂交法确定AdV复制和隔离的位置 在实验感染的成年水貂中。在受感染的成年水貂中， ADV复制的靶细胞只能在淋巴组织中找到 器官。这些细胞(占总数的2%)位于 生发中心的中心，散布在整个肠系膜 淋巴结皮层；提示B细胞细胞的分布 血统。然而，复制的数量和比例 每个感染细胞中的中间体(RF DNA、mRNA和VDNA) 与我们允许的细胞病毒系统截然不同 之前研究过的；所有3种物质的水平都至少降低了一个 因子10，Rf的量不成比例地降低。 这些结果使我们得出结论，这些人中的感染 靶细胞受到某种机制的限制。此外， 随着感染进展到慢性状态，细胞复制病毒 变得无法检测，这表明这个数字要么是 极低(大于1/105)或限制 逐渐变得更加严重。对病毒复制的限制和 ADV感染的淋巴细胞的转录可能提供了一种 免疫紊乱的发生机制和 持续感染的维持。大量的病毒粒子 在生发中心的外围以分布的方式隔离 与处理过的抗原非常相似，可能提供了一种 对观察到的极端抗病毒抗体反应的解释 在这些动物身上。抗病毒抗体可能是重要的 持续感染的发展，因为ADV的治疗 感染了特异性抗体的水貂套件将高度转化为 肺泡II型细胞被允许感染到 类似于上面描述的限制性的。

The scope of this project is the study of infections of mink with the Aleutian mink disease parvovirus (ADV). In the past year we have extended the use of strand-specific in situ molecular hybridization to define sites of ADV replication and sequestration in experimentally infected adult mink. In infected adult mink, target cells for ADV replication could be found only in lymphoid organs. These cells (up to 2% of total) were located in the centers of germinal centers and scattered throughout the mesenteric lymph node cortex; a distribution suggestive of cells of the B-cell lineage. However, the amounts and ratios of replicative intermediates (RF DNA, mRNA and vDNA) in each infected cell dramatically differed from the permissive cell-virus systems we previously studied; the levels of all 3 were damped by at least a factor of 10 and the amount of RF was disproportionately decreased. These results have led us to conclude that infection in these target cells was being restricted by some mechanism. Furthermore, as infection progressed to a chronic state, cells replicating virus became undetectable, suggesting that the number was either extremely low (greater 1/105) or that the restriction was progressively more severe. A restriction on viral replication and transcription in ADV infected lymphoid cells might provide a mechanism for the development of immune disorders and for the maintenance of persistent infection. Large amounts of virions were sequestered in the periphery of germinal centers in a distribution very similar to that of processed antigen, possibly providing an explanation for the extreme antiviral antibody response observed in these animals. Antiviral antibody may be important in the development of persistent infection, because treatment of ADV infected mink kits with specific antibody converted the highly permissive infection of the alveolar type II cells into a restrictive one similar to that described above.