PATHOGENESIS OF ALEUTIAN DISEASE VIRUS INFECTION

本项目的目的是研究水貂阿留申病， 阿留申病细小病毒（ADV）的持续感染。 我们有 扩展研究，包括使用作为杂交的原位杂交 探针放射性标记的分子克隆的ADV DNA。 细胞培养中的复制 伴随着核病毒抗原的发展， 感染细胞核上放射自显影颗粒的数量。 这 结果与感染水貂组织中的发现形成明显对比。 在脾脏和肠系膜淋巴结（MLN）中，ADV DNA易于检测 主要存在于细胞质或细胞膜上。 更以 MLN颗粒被发现局限于周边的germinal中心在一个 网状模式，使人联想到蛋白质抗原所描述的 免疫后。 由于病毒抗原在不同的组织中有相同的分布， 这表明，观察到的DNA可能代表了 病毒颗粒被免疫系统的元素隔离，而不是 病毒复制的场所。 罕见的单细胞含有颗粒， 这一观察结果表明， 在这些组织中复制的ADV很小。 广泛尝试 通过体外培养感染的细胞来表征感染的细胞， ADV复制不能令人信服地证明 虽然淋巴细胞用有丝分裂原和貂T细胞刺激， 生长因子 这些结果表明ADV的靶细胞是 或者不是淋巴细胞，或者其体外培养的条件 是非常挑剔的 在其他研究中，干扰素在肿瘤发病机制中的可能作用 ADV感染已经开始。 细胞培养中ADV感染诱导 干扰素在31.8摄氏度和37摄氏度，虽然诱导 在37 ℃时比在31.8 ℃时快得多。 因为 ADV仅在较低温度下复制，这一发现可能表明 干扰素在抑制ADV复制中的潜在作用 37摄氏度。

The purpose of this project is the study of Aleutian disease (AD) of mink, a persistent infection by the Aleutian disease parvovirus (ADV). We have extended studies to include in situ hybridization using as hybridization probe radiolabeled molecularly cloned ADV DNA. Replication in cell culture was accompanied by the development of nuclear viral antigen and large numbers of autoradiographic grains over the nuclei of infected cells. This result contrasted markedly with findings made in tissues of infected mink. In spleen and mesenteric lymph node (MLN), ADV DNA was readily detected primarily in the cytoplasm or on the membranes of cells. Furthermore, in MLN grains were found localized to the periphery of germinal centers in a reticular pattern reminiscent of that described for protein antigens following immunization. Since viral antigens had the same distribution in these sections, this suggested that the DNA observed probably represented virus particles sequestered by elements of the immune system rather than sites of virus replication. Rare single cells contained grains localized over the nucleus, and this observation implied that the number of cells actually replicating ADV in these tissues was small. Extensive attempts were made to characterize infected cells by culturing infected in viro or in vivo with ADV. ADV replication could not be convincingly demonstrated although the lymphocytes were stimulated with mitogens and mink T cell growth factor. These results suggested that the target cell for ADV is either not a lymphocyte or that the conditions for its cultivation in vitro are exremely fastidious. In other studies, the possible role of interferons in the pathogenesis of ADV infections has been begun. ADV infection in cell culture induces interferon at both 31.8 degrees C and 37 degrees C, although the induction at 37 degrees C is much more rapid than that at 31.8 degrees C. Because ADV replicates only at the lower temperature, this finding may suggest a potential role for interferon in the suppression of ADV replication at 37\degrees C.