Functional Analysis of FIV ORF-A

FIV ORF-A 的功能分析

• 批准号: 6746931
• 负责人: AYALEW MERGIA
• 金额: $ 25.46万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6746931
• 关键词: B lymphocyte; HIV infections; T lymphocyte; cats; cell sorting; cellular immunity; feline immunodeficiency virus; gene expression; gene mutation; genetic promoter element; genome; helper T lymphocyte; immunosuppression; nucleic acid repetitive sequence; open reading frames; polymerase chain reaction; protein protein interaction; suppressor T lymphocyte; thymus; tissue /cell culture; virus cytopathogenic effect; virus infection mechanism; virus protein; virus replication; yeast two hybrid system

DESCRIPTION (provided by applicant):Feline immunodeficiency virus (FIV), a lentivirus of cats, causes an AIDS similar to what is seen in humans with human immunodeficiency virus (HIV). The clinical course of FIV infection parallels HIV infection in humans. A few weeks after experimental infection with FIV, cats develop an acute clinical syndrome like the HIV infection, including low-grade fever and transient generalized lymph node enlargement. This is followed by a long asymptomatic period in which the CD4+:CD8+ cell ratio declines because of a gradual decrease in CD4+ cells, and an increase in CD8+ cells as well. Similar to HIV, the FIV genome contains several open reading frames (ORFs) in addition to genes encoding for the structural proteins. The ORF-A gene product transactivates FIV promoter-dependent gene expression in vitro. Infection studies with ORF-A defective FIV show that virus replication is reduced both in vitro and in vivo. In cats infected with ORF-A defective FIV the onset of reduced peripheral blood CD4:CD8 ratio is delayed. Comparison of thymocyte subpopulations demonstrated a reduced expansion of single positive CD4-CD8+ thymocytes in ORF-A defective FIV infected cats. The observation that there is a reduction in virus replication and delay of the onset of parameters that measure immunodeficiency in cats infected with an ORF-A defective mutant suggests that this protein is important in the progress of disease caused by FIV. By determining the level of viral gene expression in different primary cells in the presence and absence of ORF- A, we will define the role of ORF-A in controlling the cell tropism and cytopathology. These studies in combination with dissection of functional characterization of the ORF-A will clarify the role of ORF-A in FIV pathogenesis.

描述（由申请方提供）：猫免疫缺陷病毒（FIV）是猫的一种慢病毒，可引起与人类免疫缺陷病毒（HIV）相似的艾滋病。FIV感染的临床过程与人类HIV感染相似。实验性感染FIV后几周，猫会出现类似HIV感染的急性临床综合征，包括低热和一过性全身淋巴结肿大。随后是一个很长的无症状期，其中CD 4+：CD 8+细胞比例下降，因为CD 4+细胞逐渐减少，CD 8+细胞也增加。与HIV类似，FIV基因组除了编码结构蛋白的基因外，还含有几个开放阅读框（ORF）。ORF-A基因产物在体外反式激活FIV启动子依赖性基因表达。 用ORF-A缺陷型FIV进行的感染研究表明，病毒复制在体外和体内均减少。在感染有ORF-A缺陷的FIV的猫中，外周血CD 4：CD 8比率降低的发作被延迟。 胸腺细胞亚群的比较表明，在ORF-A缺陷型FIV感染的猫中，单个阳性CD 4-CD 8+胸腺细胞的扩增减少。观察到病毒复制减少和测量感染ORF-A缺陷突变体的猫的免疫缺陷的参数的发生延迟，表明这种蛋白质在由FIV引起的疾病的进展中是重要的。通过测定在存在和不存在ORF-A的情况下不同原代细胞中病毒基因的表达水平，我们将确定ORF-A在控制细胞嗜性和细胞病理学中的作用。这些研究结合ORF-A的功能特征的解剖将阐明ORF-A在FIV发病机制中的作用。