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: 3818225
• 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/3818225
• 关键词: AIDS; Retroviridae; Retroviridae disease; antibody formation; antibody neutralization test; antibody specificity; antiviral antibody; blood cells; disease /disorder model; equine infectious anemia virus; genetic recombination; genetic strain; hemolytic anemia; horses; immunoprecipitation; immunosuppression; microorganism immunology; molecular cloning; monoclonal antibody; mutant; virus DNA; virus antigen; virus classification; virus diseases; virus genetics; virus infection mechanism; virus replication

Equine infectious anemia virus (EIAV) is morphologically, genetically, and serologically related to human immunodeficiency virus (HIV) and thus provides a useful model for the study of virus-host interactions in lentivirus-induced disease. Characteristic of equine infectious anemia (EIA) is the episodic nature of clinical disease which is associated with the appearance of novel viral variants. This project is concerned with elucidating the factors important in the generation and selection of these viral variants and in understanding the role of variation in lentivirus persistence and pathogenesis. Our previous work suggested that early in the course of disease, EIAV variants may be selected in vivo by non-immunological mechanisms. We have therefore initiated studies on the in vitro host cell tropism of various strains of EIAV and its possible correlation with viral pathogenicity. Virus isolated which were selected for in vitro replication in continuous cell lines demonstrated a 1,000-10,000- fold reduction in viral replication in primary horse monocyte cultures (HMC) as compared to replication in continuous cell lines. Moreover, this marked reduction of viral replication in horse monocytes, believed to be the target cell for EIAV replication in vivo, was associated with a loss of viral virulence. This suggest that levels of viral replication in in vitro HMC may be a correlate of in vivo pathogenicity. Thus, we have increased our efforts to isolate a replication-competent molecular clone of EIAV which could serve as a basis for understanding structural viral features important in viral pathogenicity.

马传染性贫血病毒（EIAV）是一种形态学上， 在遗传学和血清学上与人类免疫缺陷 病毒（HIV），从而提供了一个有用的模型， 慢病毒诱导疾病中的病毒-宿主相互作用。 马传染性贫血（EIA）的特点是发作性， 与外观相关的临床疾病的性质 新的病毒变种。 本项目涉及 阐明产生和选择中的重要因素 了解这些病毒变异并了解变异的作用 慢病毒的持久性和致病性。 我们以前的工作 提示在疾病早期，EIAV变异体可能 通过非免疫机制在体内选择。 我们有 因此，启动了体外宿主细胞嗜性的研究， EIAV的不同毒株及其与病毒的可能相关性 致病性 选择用于体外试验的病毒分离物 在连续细胞系中的复制证明了1，000 - 10，000- 原代马单核细胞中病毒复制减少倍数 与在连续细胞系中复制相比，在HMC培养物中复制的细胞数量增加。 此外，这种显著减少病毒复制在马， 单核细胞，被认为是EIAV复制的靶细胞， 体内，与病毒毒力的丧失有关。 这表明 体外HMC中的病毒复制水平可能与 体内致病性。 因此，我们加大了努力， 分离出一个具有复制能力EIAV分子克隆， 作为理解病毒结构特征的基础 在病毒致病性中起重要作用。