IMMUNE CONTROL OF EQUINE INFECTIOUS ANEMIA LENTIVIRUS

非致癌逆转录病毒的慢病毒亚家族的成员 导致人类和动物的持续感染， 或复发性疾病。 尽管疾病的类型可以包括 免疫缺陷，贫血，关节炎，脑炎和肺炎， 慢病毒共有几个生物学特征。 他们不会被淘汰， 感染宿主并建立宿主细胞的潜伏感染，特别是 单核细胞 通过持续感染的宿主细胞表达慢病毒 由于env基因序列的改变， 逃避免疫反应的变异。 据设想， 一系列的研究目标是确定病毒之间的分子相互作用 和淋巴细胞，导致控制马慢病毒，马， 传染性贫血病毒（EIAV），将提供有价值的信息， 控制人类免疫缺陷病毒和其他动物慢病毒。 马传染性贫血病毒感染的马有反复发作的临床疾病 与由独特抗原变体引起的无细胞病毒血症相关。 大多数受感染的马在感染后几天内控制每次病毒血症发作。 它的外观。 在感染后的几个月内，幸存的马 独特地控制所有无细胞病毒血症和疾病的发生。 它有 已经证明EIA病毒血症的控制是由特异性的 免疫反应的马传染性贫血病毒感染遗传免疫缺陷的马。 确定刺激特异性免疫的病毒表位 控制EIAV所需的反应，假设 EIAV携带者的临床静止状态由细胞毒性T细胞维持， 淋巴细胞，并且这种CTL应答可以通过免疫诱导， 通过追求4个具体目标进行测试： 1. 抑制EIAV携带马的EqCD8淋巴细胞功能， 确定是否发生病毒血症和临床疾病。 2. 鉴定EIAV蛋白并确定CTL识别的表位， 载体 马 3. 用重组痘苗病毒诱导马的CTL 定义 EIAV蛋白的表位。 4. 马传染性贫血病毒同源株和抗原株攻毒免疫马的研究 变体。

The lentivirus subfamily of nononcogenic retroviruses has members that cause persistent infection of humans and animals resulting in progressive or recurrent disease. Even though the type of disease can include immunodeficiency, anemia, arthritis, encephalitis, and pneumonia, the lentiviruses share several biologic features. They are not eliminated from infected hosts and establish latent infection of host cells, particularly monocytes. Expression of lentiviruses by persistently infected host cells is enhanced by changes in the env gene sequence resulting in antigenic variants that escape the immune response. It is envisioned that the long range research goal of defining the molecular interactions between virus and lymphocytes that result in the control of a horse lentivirus, equine infectious anemia virus (EIAV), will provide valuable information for the control of human immunodeficiency virus and other animal lentiviruses. Horses with EIAV infection have recurrent episodes of clinical disease associated with cell-free viremia caused by unique antigenic variants. Most infected horses control each viremic episode within a few days after its appearance. Within a few months after infection, surviving horses uniquely control all occurrences of cell-free viremia and disease. It has been demonstrated that the control of EIA viremia is mediated by specific immune responses by infecting genetically immunodeficient horses with EIAV. To define the virus epitopes that stimulate the specific immune responses required to control EIAV, the hypothesis that the clinically-quiescent state in EIAV carriers is maintained by cytotoxic T lymphocytes and that this CTL response can be induced by immunization will be tested by pursuing 4 specific aims: 1. Inhibit EqCD8 lymphocyte function in EIAV carrier horses and determine if viremia and clinical disease occur. 2. Identify EIAV proteins and define epitopes recognized by CTL from carrier horses. 3. Induce CTL in horses with vaccinia virus recombinants expressing defined epitopes of EIAV proteins. 4. Challenge immunized horses with homologous EIAV and with antigeni variants.