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

抗原变异被认为是一种手段，通过这种手段 慢病毒，包括马传染性贫血病毒(EIAV)，艾滋病 逆转录病毒和Visna病毒，能够在 病毒特异性宿主免疫反应。这个项目的目标是 阐明遗传基因的产生和选择中的重要因素 与EIAV的抗原变异体有关的变异在 病毒的持久性和疾病的致病机制。我们回收了几株 来自两个早期临床疾病周期的实验性EIAV 受感染的马。这些分离株被发现是遗传变异，如 经RNaseT1抗性寡核苷酸指纹分析确定。 此外，这些分离株可以通过抗体在抗原性上区分开来。 它结合在感染病毒的细胞表面，支持这一概念 识别新出现的病毒的抗体的顺序发展 变种。然而，在早期，没有检测到中和抗体， 分离出这些变异体的发热期。相反， 中和抗体在病程较晚时被检测到，但 针对后来出现的病毒变异株的中和抗体是 在中和较早出现的特异性抗体之前进行检测 变种。这些结果表明，中和可能不是 选择EIAV变种的机制。然而，非中和 抗病毒抗体仍有可能通过识别和筛选变异体 消除某些受病毒感染的细胞。或者，抗体 特异性可能是对病毒变异的反应，而不是原因 在活体内。为了更清楚地定义抗体在人类免疫反应中的作用 选择病毒变异体，我们计划分析其遗传和抗原性 6株EIAV分离株的亲缘关系分析 实验感染的马的发热期。

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.