FOAMY VIRUS INFECTION IN VITRO AND IN VIVO

体外和体内泡沫病毒感染

• 批准号: 6688244
• 负责人: Maxine L Linial
• 金额: $ 29.24万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-05 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6688244
• 关键词: Retroviridae; Retroviridae disease; fluorescent in situ hybridization; genetic promoter element; host organism interaction; laboratory mouse; microorganism culture; microorganism immunology; nucleic acid repetitive sequence; polymerase chain reaction; provirus; transfection /expression vector; virus genetics; virus infection mechanism; virus protein; virus replication

DESCRIPTION:(Adapted from the Investigator's abstract): Foamy viruses are complex retroviruses with replication pathways which differ greatly from those of the conventional retroviruses such as oncoviruses or lentiviruses. The prototype foamy virus is HFV, which was isolated from a human cell line, but which is virtually identical to a chimpanzee virus. Foamy viruses are not prevalent in human populations, but humans can be infected through contact with primates. The course of infection by HFV and other foamy viruses is distinct from that of the other retroviral genera in that a life long, persistent, apparently benign, infection ensues. Virus can often be isolated decades after initial infection. This is true for both natural hosts, such as primates, cats or cows, and accidentally infected hosts such as humans. In vitro, HFV is highly cytopathic in some cell types, yet persistent infection ran be obtained in other cells. Little is known about the difference in host cell response. The goal of this proposal is to use both permissive and persistent cells in culture, and a mouse model to dissect the contributions of viral gene products and the host immune system in establishment of benign persistent infections. Immune competent mice can be infected with HFV without ensuing pathology. Three specific aims are proposed. 1. To characterize HFV infections in vitro in a variety of cell lines and normal cell types. These experiments will define the host range of the virus, including the cell types in which virus can integrate. 2. To determine the role of the viral non-structural protein Bet, as well as that of the two viral promoters in the outcome of infection (persistent vs. permissive). 3. To characterize of the host immune response to the virus. In vitro assays will be used to study T cell responses to viral infection. The course and ultimate outcome of infection in wt and immune deficient mice will be assessed. This set of experiments should help determine whether the absence of pathogenicity in normal animals is a function of the viral replication pathway, specific host defenses, or both. These experiments will be will be important for the assessment of the utility of foamy viruses as vectors for gene therapy.

描述：（改编自研究者摘要）：泡沫病毒是 复制途径与那些复制途径大不相同的复杂逆转录病毒 如肿瘤病毒或慢病毒。的 泡沫病毒的原型是HFV，它是从人类细胞系中分离出来的，但 和黑猩猩病毒几乎一样泡沫病毒不是 在人群中流行，但人类可通过接触 灵长类动物HFV和其他泡沫病毒的感染过程是不同的 与其他逆转录病毒属不同的是， 表面上是良性的，但感染是恶性的。病毒通常可以在几十年后分离出来 初始感染。这对两种自然宿主都是如此，如灵长类动物、猫 或牛，以及意外感染的宿主，如人类。在体外，HFV是 在某些细胞类型中高度致细胞病变，但仍能获得持续感染 在其他细胞。对宿主细胞反应的差异知之甚少。的 该提案的目标是同时使用许可和持久单元， 培养和小鼠模型来剖析病毒基因产物的贡献 以及宿主免疫系统在良性持续感染的建立中的作用。 免疫活性小鼠可以感染HFV而不发生病理学改变。三 提出了具体目标。1.为了在体外表征HFV感染， 多种细胞系和正常细胞类型。这些实验将定义 病毒的宿主范围，包括病毒可以整合的细胞类型。 2.为了确定病毒非结构蛋白Bet的作用，以及 两种病毒启动子在感染结果中的作用（持续性vs. 许可的）。3.表征宿主对病毒的免疫反应。在 体外试验将用于研究T细胞对病毒感染的应答。的 WT和免疫缺陷小鼠中感染的过程和最终结果将 被评估。这组实验应该有助于确定 在正常动物中的致病性是病毒复制的功能 途径，特定的宿主防御，或两者。这些实验将是 重要的是评估泡沫病毒作为载体的效用， 基因治疗