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

马传染性贫血病毒（艾滋病逆转录病毒模型）的免疫生物学

• 批准号: 3960601
• 负责人: B CHESEBRO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3960601
• 关键词: AIDS; Retroviridae; antibody formation; antibody neutralization test; antibody specificity; antiviral antibody; blood cells; disease /disorder model; equine infectious anemia virus; genetic recombination; genetic strain; hemolytic anemia; immunosuppression; microorganism immunology; monoclonal antibody; mutant; virus antigen; virus diseases; virus genetics; virus infection mechanism

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.

抗原变异被认为是一种方法， 慢病毒，包括马传染性贫血病毒（EIAV）、艾滋病病毒 逆转录病毒和visna病毒，能够持续存在，尽管 病毒特异性宿主免疫应答。 该项目的目标是 阐明了遗传物质的产生和选择中的重要因素， 和EIAV的抗原变异体， 病毒的持久性和疾病的发病机制。 我们分离出了 EIAV从两个早期周期的临床疾病在一个实验性的 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，还可通过抗体对分离株进行抗原性区分 与病毒感染细胞的表面结合， 一种能识别新出现的病毒的抗体 变体。 然而，在早期， 这些变异体被分离出来的发热期。 相反地， 中和抗体在病程后期检测到，但 对后来出现的病毒变异体具有特异性的中和抗体， 在中和早期出现的特异性抗体之前检测到 变量。 这些结果表明，中和可能不是 EIAV变异体的选择机制。 然而，非中和 抗病毒抗体仍然可以通过识别来选择变体， 清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 in vivo. 为了更清楚地定义抗体在免疫中的作用， 选择病毒变体，我们计划分析基因和抗原性， 我们从连续感染的6株EIAV分离株中， 实验感染的马的发热期。