Regulation of HIV-1 Host Factor Interactions by Cyclophilin A

亲环蛋白 A 对 HIV-1 宿主因子相互作用的调节

• 批准号: 8603170
• 负责人: Mallori Jacole Burse
• 金额: $ 2.68万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8603170
• 关键词: Binding; Binding Proteins; Biological Assay; Capsid; Capsid Proteins; Cells; Cercopithecidae; Cyclophilin A; Cyclosporine; Dependence; Disease; Drug Targeting; Fibrinogen; HIV-1; Hela Cells; Human; In Vitro; Infection; Integration Host Factors; Jurkat Cells; Mass Spectrum Analysis; Measures; Mediating; Mediator of activation protein; Mutation; N-terminal; Nuclear; Peptidylprolyl Isomerase; Pharmaceutical Preparations; Phenotype; Protein Binding; Proteins; Proteomics; Recombinants; Regulation; Research; Reverse Transcription; Role; Small Interfering RNA; Suggestion; TRIM Motif; Testing; Validation; Viral; Virus; Work; base; cofactor; comparative; heterokaryon; in vivo; inhibitor/antagonist; multicatalytic endopeptidase complex; mutant; nonhuman primate; novel; pathogen; premature; public health relevance; virus host interaction

DESCRIPTION (provided by applicant): The HIV-1 capsid is an important determinant of viral replication. Early studies demonstrated the intrinsic importance of the capsid in mediating uncoating of the viral core. More recently, the capsid has emerged as an important mediator of virus-host interactions. Cyclophilin A (CypA) is an abundant cellular protein known to bind the N-terminal domain of the capsid protein. CypA can promote infection of some HIV-1 strains in certain cells, but it can also inhibit infection. Despite many years of research, we still do not understand these mechanisms. I hypothesize that CypA modulates HIV-1 infection by regulating the interaction of specific cellular proteins with the HIV-1 capsid. Indeed, we have observed that CypA can regulate the non-human primate capsid-binding restriction factor, TRIM5¿. However, the mechanism of this activity is poorly understood. I will determine the ability of CypA to regulate capsid-binding restriction factors by i) elucidating the mechanism of CypA-dependent TRIM5¿ restriction and ii) determining the ability of CypA to alter the capsid interactome using comparative proteomics.

描述（由申请方提供）：HIV-1衣壳是病毒复制的重要决定因素。早期的研究证明了衣壳在介导病毒核心的脱壳中的内在重要性。最近，衣壳已成为病毒-宿主相互作用的重要介质。亲环素A（CypA）是已知结合衣壳蛋白的N-末端结构域的丰富的细胞蛋白。CypA可以促进某些HIV-1毒株在某些细胞中的感染，但它也可以抑制感染。尽管经过多年的研究，我们仍然不了解这些机制。我推测CypA通过调节特定细胞蛋白与HIV-1衣壳的相互作用来调节HIV-1感染。事实上，我们已经观察到CypA可以调节非人灵长类动物的captain结合限制因子TRIM 5？。然而，这种活动的机制知之甚少。我将确定CypA调节衣壳结合限制因子的能力，通过i）阐明CypA依赖性TRIM 5？限制的机制和ii）使用比较蛋白质组学确定CypA改变衣壳相互作用组的能力。