PATHOGENESIS OF BIV-INDUCED LYMPHOPROLIFERATIVE CHANGES

本研究的主要目的是描述 可能影响病毒复制和淋巴组织增生性变化 牛免疫缺陷样病毒（BIV）感染引起的。 待研究的因素包括病毒遗传变异、 抗体应答，与牛白血病病毒（BLV）共感染，以及 免疫抑制 BIV是一种慢病毒， 牛的淋巴组织增生性变化， 与HIV-1相关的抗原。 BLV是一种肿瘤病毒， 牛白血病和淋巴肉瘤，结构类似于 HTLV-1。 该项目的一个主要目标是确定是否在体内或在 BIV和BLV的体外共感染改变了复制或 任何一种病毒的致病机理。 被感染的动物 BIV、BLV或BIV和BLV都将继续从2 通过感染后6年的病毒复制， 抗体应答、免疫能力以及临床和血液学 变化 连续病毒分离株和血清样品从这些 动物的特征在于抗原特异性， 与体内病毒复制相关。 BIV与 将通过定量表征体外共感染细胞中的BLV 无细胞病毒，监测病毒调节因子的表达， 蛋白质，和使用异源病毒启动子的反式激活 瞬时表达测定。 病毒变异在 BIV的发病机制将通过比较体内 病理效应和细胞嗜性， 病毒基因组的调控、结构和包膜序列。 的 BIV和HIV-1之间以及BLV和HTLV-1之间的相似性表明， 这些是非常有前途的家畜模型， 逆转录病毒相关的人类恶性肿瘤。 描述了各种 上述因子有助于调节BIV病毒 复制和诱导淋巴增生性变化将有助于 对逆转录病毒引起的淋巴组织增生性疾病有基本认识。

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.