IMMUNOBIOLOGY OF EQUINE INFECTIOUS ANEMIA VIRUS, A RETROVIRUS MODEL FOR AIDS

抗原变异已被建议作为一种手段 慢病毒，包括马传染性贫血病毒 (EIAV)、艾滋病 逆转录病毒和维斯纳病毒，尽管存在 病毒特异性宿主免疫反应。 该项目的目标是 阐明遗传基因的产生和选择的重要因素 以及 EIAV 的抗原变体关于变异的作用 病毒的持续存在和疾病的发病机制。 我们回收了分离株 EIAV 来自两个早期临床疾病周期的实验 被感染的马。 这些分离株被发现是遗传变异 通过 RNase T1 抗性寡核苷酸指纹分析确定。 此外，分离株可以通过抗体进行抗原区分 它与病毒感染细胞的表面结合，支持了这一概念 识别新兴病毒的抗体的连续开发 变体。 然而，在早期，没有检测到中和抗体， 从中分离出这些变体的发热期。 相反， 中和抗体是在病程后期检测到的，但是 对后来出现的病毒变种具有特异性的中和抗体是 在中和针对早期出现的特异性抗体之前检测到 变体。 这些结果表明中和可能不是 选择 EIAV 变体的机制。 然而，非中和 抗病毒抗体仍可能通过识别和识别来选择变异体 消除某些病毒感染的细胞。 或者，抗体 特异性可能是对病毒变异的反应，而不是病毒变异的原因 体内。 试图更清楚地定义抗体在 选择病毒变体，我们计划分析遗传和抗原 我们从连续检测中发现的 6 种 EIAV 分离株的相关性 实验感染马的发热期。

Antigenic variation has been suggested as a meas by which several lentiviruses, including equine infectious anemia virus (EIAV), AIDS retrovirus and visna virus, are able to persist in spite of a virus-specific host immune response. The goal of this project is to elucidate the factors important in the generation and selection of genetic and antigenic variants of EIAV with regard to the role of variation in viral persistence and the pathogensis of disease. We recovered isolates of EIAV from two early cycles of clinical disease in an experimentally infected horse. These isolates were found to be genetic variants as determined by RNase T1 resistant oligonucleotide fingerprint analysis. Furthermore, the isolates could be antigenically distinguished by antibody which bound to the surface of virus-infected cells, supporting the concept of a sequential development of antibody which recognizes emerging viral variants. However, no neutralizing antibody was detected during the early, febrile periods from which these variants were isolated. Instead, neutralizing antibody was detected later in the course of disease, but neutralizing antibody specific for the later appearing virus variant was detected prior to neutralizing antibody specific for the earlier appearing variant. These results suggested that neutralization might not be the mechanism for selection of EIAV variants. However, non-neutralizing antiviral antibody might still select for variants through recongition and elimination of certain virus-infected cells. Alternatively, the antibody specificity may be a response to, rather than a cause of, viral variation in vivo. In an attempt to more clearly define the role of antibody in the selection of viral variants, we plan to analyze the genetic and antigenic relatedness of six isolates of EIAV which we recovered from consecutive febrile periods of an experimentally infected horse.