PATHOGENESIS OF BIV-INDUCED LYMPHOPROLIFERATIVE CHANGES

这项研究的主要目的是描述 可能影响病毒复制和淋巴增殖性改变 由牛免疫缺陷样病毒(BIV)感染引起的牛。 需要研究的因素包括病毒的遗传变异、病毒的特异性 抗体反应，与牛白血病病毒(BLV)的混合感染，以及 免疫抑制。BIV是一种慢病毒，它能引起轻微的 牛的淋巴增殖性变化，遗传和 与HIV-1抗原性相关。BLV是一种已知是致病原因的肿瘤病毒 牛白血病和淋巴肉瘤，在结构上类似于 HTLV-1。这个项目的一个主要目标是确定体内或体内 BIV和BLV体外混合感染改变复制或 任何一种病毒的致病机理。被感染的动物 BIV、BLV或同时监控BIV和BLV将从2开始继续 通过感染后6年的病毒复制，特异性 抗体应答、免疫能力与临床和血液学 改变。从这些地方获得的连续病毒分离株和血清样本 动物将被定性为抗原特异性，并将被 与体内的病毒复制有关。BIV和BIV的相互作用 BLV在体外共感染细胞中的特征将通过定量 无细胞病毒，监测病毒调控基因的表达 蛋白质和异源病毒启动子的反式激活 瞬时表达分析。病毒变异在人类免疫缺陷中的作用 BIV的发病机制将通过比较体内差异来研究 遗传差异在体外的病理效应和细胞趋向性 病毒基因组的调控序列、结构序列和包膜序列。这个 BIV和HIV-1以及BLV和HTLV-1之间的相似性表明 这些都是非常有希望的家养动物模型 与逆转录病毒相关的人类恶性肿瘤。描述各种不同的 上述因素有助于对BIV病毒的调控 淋巴增生性改变的复制和诱导将有助于 基本了解逆转录病毒引起的淋巴增生性疾病。

The primary objective of this research is to characterize factors which may influence viral replication and the lymphoproliferative changes induced by bovine immunodeficiency-like virus (BIV) infection in cattle. Factors to be studied include viral genetic variation, specificity of the antibody response, co-infection with bovine leukemia virus (BLV), and immunosuppression. BIV is a lentivirus which induces mild lymphoproliferative changes in cattle and is genetically and antigenically related to HIV-1. BLV is an oncovirus known to be a cause of bovine leukemia and lymphosarcoma and is structurally similar to HTLV-1. A major goal of this project is to determine if in vivo or in vitro co-infection with BIV and BLV alters the replication or pathogenesis of either virus. Animals which have been infected with either BIV, BLV, or both BIV and BLV will continue to be monitored from 2 through 6 years post infection for virus replication, specificity of the antibody response, immune competence and clinical and hematologic changes. Sequential virus isolates and serum samples obtained from these animals will be characterized as to antigenic specificity and will be correlated with viral replication in vivo. The interaction of BIV and BLV in co-infected cells in vitro will be characterized by quantitation of cell free virus, monitoring for expression of viral regulatory proteins, and transactivation of heterologous virus promoters using transient expression assays. The role of viral variation in the pathogenesis of BIV will be studied by comparing differences in in vivo pathologic effects and cell tropism in vitro with genetic differences in regulatory, structural, and envelop sequences of the viral genome. The similarities between BIV and HIV-1 and between BLV and HTLV-1 suggest that these are very promising domestic animal models for retroviral-associated human malignancies. Characterizing how the various factors described above contribute to the regulation of BIV viral replication and induction of lymphoproliferative changes will help in the basic understanding of retroviral-induced lymphoproliferative diseases.