IMMUNE CONTROL OF EQUINE INFECTIOUS ANEMIA LENTIVIRUS

慢病毒亚家族的非致癌逆转录病毒具有 引起人和动物的持续感染，导致进行性 或反复发作的疾病。即使疾病的类型可能包括 免疫缺陷、贫血、关节炎、脑炎和肺炎， 慢病毒有几个共同的生物学特征。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。慢病毒在持续感染宿主细胞中的表达 通过env基因序列的改变而增强，从而导致抗原性 逃脱免疫反应的变种。据设想，长城 确定病毒之间分子相互作用的范围研究目标 以及导致控制马慢病毒的淋巴细胞，马 传染性贫血病毒(EIAV)的发现，将为 控制人类免疫缺陷病毒和其他动物慢病毒。 感染EIAV的马有反复发作的临床疾病 与由独特的抗原变异引起的无细胞病毒血症有关。 大多数受感染的马在感染病毒后几天内控制了每一次病毒发作 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 已证明EIA病毒血症的控制是由特异性介导的 通过感染EIAV感染遗传免疫缺陷的马的免疫反应。 确定刺激特定免疫的病毒表位 控制EIAV所需的反应，假设 EIAV携带者的临床静止状态是由细胞毒性T细胞维持的 淋巴细胞和这种CTL反应可以通过免疫诱导 通过追求4个具体目标来进行测试： 1.抑制EIAV携带者的EqCD8淋巴细胞功能 确定是否出现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 马匹。 3.用痘苗病毒重组表达载体诱导马的CTL 已定义 EIAV蛋白的表位。 4.用同源EIAV和抗原攻击免疫的马 变种。

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.