PATHOGENESIS OF ALEUTIAN DISEASE VIRUS INFECTION

这个项目的范围是阐明致病机制涉及 水貂阿留申病细小病毒（ADV）感染。 在过去的一年里，我们继续研究ADV在 巨噬细胞 ADV基因组的表达和复制是 在源自成人的原代腹膜巨噬细胞培养物中检查 貂皮。 一小部分巨噬细胞感染了病原体 ADV-Utah 1表达ADV，而ADV-G不表达ADV 感染后的抗原。 ADV-Utah制备的DNA分析 1例感染的巨噬细胞显示ADV的明确扩增 基因组和ADV DNA复制形式（RF）的存在，但 基因表达水平太低，无法定义特定的 Western blot检测病毒蛋白。 还发现了几种人单核细胞系（U-937和THP-1 以支持ADV-Utah 1表达，并且表达可以是 通过用巨噬细胞分化诱导剂处理来调节。 病毒不能在U-937细胞中连续增殖，因此感染 不是完全允许的，而是如在体内所见受到限制的 感染. 存在ADV DNA的各种复制形式，但 单链病毒体DNA相对水平似乎较低 而不是被允许感染的细胞。 两种衣壳蛋白和 感染的U937细胞中存在主要的非结构蛋白NS-1。 观察到三种大小的病毒mRNA，但2.8kb的病毒mRNA在2.8kb的病毒mRNA中被观察到。 这些细胞中的mRNA带可分为两个明确的组分， 与允许感染的细胞略有不同。 这一发现可能 反映了较小的NS-2蛋白表达的变化， 允许和限制性ADV感染。 水貂淋巴结培养物被发现表达生物活性IL-6，但 水貂IL-6的基因尚未克隆。 此外，U937细胞 感染ADV-Utah 1，但不感染ADV-G，产生人IL-6。

The scope of this project is to elucidate pathogenic mechanisms involved in infections of mink with Aleutian mink disease parvovirus (ADV). In the past year we continued studies on the replication of ADV in macrophages. Expression and replication of the ADV genome was examined in primary peritoneal macrophage cultures derived from adult mink. A small percentage of macrophages infected with the pathogenic ADV-Utah 1, but not the cell culture adapted ADV-G, expressed ADV antigens following infection. Analysis of DNA prepared from ADV-Utah 1 infected macrophages revealed definite amplification of the ADV genome and the presence of ADV DNA replicative forms (RF), but the level of gene expression was too low to allow the definition of specific viral proteins by Western blot. Several human monocyte cell lines (U-937 and THP-1) were also found to support ADV-Utah 1 expression and the expression could be modulated by treatment with an inducer of macrophage differentiation. Virus could not be serially propagated in U-937 cells, thus the infection was not fully permissive, but was restricted as is seen in vivo infections. The various replicative forms of ADV DNA were present, but the relative level of single stranded virion DNA appeared to be lower than in permissively infected cells. The 2 capsid proteins and the major nonstructural protein, NS-1, were present in infected U937 cells. The three size classes of viral mRNA were observed, but the 2.8 kb mRNA band in these cells could be resolved into 2 definite components, slightly different from permissively infected cells. This finding might reflect a variation in the expression of the smaller NS-2 protein between permissive and restricted ADV infections. Mink lymph node cultures were found to express a bioactive IL-6, but the gene for mink IL-6 has not yet been cloned. In addition, U937 cells infected with ADV-Utah 1, but not ADV-G, elaborate human IL-6.