CD* T cell responses to gamma-herpesviral infection

CD* T 细胞对 γ-疱疹病毒感染的反应

• 批准号: 7929661
• 负责人: Michael L Freeman
• 金额: $ 5.05万
• 依托单位: TRUDEAU INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-16 至 2011-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7929661
• 关键词: Address; Affect; Antigens; Antiviral Agents; Appearance; Cells; Chronic; Complex; Data; Economic Inflation; Epitopes; Experimental Animal Model; Face; Gene Expression; Gene Expression Profile; Generations; Goals; Herpesviridae; Immune response; Immunity; Immunologic Surveillance; Immunoproliferative Disorders; Individual; Infection; Kinetics; Latent Virus; Lead; Lesion; Life; Location; Lytic Virus; Maintenance; Malignant Neoplasms; Mus; Pathology; Pattern; Phenotype; Recurrent disease; Regulation; Relative (related person); Reporting; Research Proposals; Rodent; Role; Satellite Viruses; Signal Transduction; Source; Specificity; T cell response; T memory cell; T-Lymphocyte; Testing; Therapeutic; Time; Transplantation; Tropism; Vaccination; Vaccine Design; Vaccines; Viral; Viral Antigens; Virus; Virus Diseases; Virus Latency; exhaustion; gammaherpesvirus; insight; latent infection; mouse model; mutant; pathogen; prevent; prophylactic; public health relevance; reactivation from latency; recombinant virus; response; therapeutic target; vaccination strategy

DESCRIPTION (provided by applicant): The majority of people worldwide are persistently infected with latent viruses. These viruses can reactivate from latency at any time, leading to recurrent diseases for the life of the host. It is currently unknown how the host immune response interacts with latent virus to prevent reactivation while preventing pathology due to overactive immunity. The goal of this research proposal is to determine the contributions of viral latency and reactivation in regulating the generation and maintenance of antiviral CDS T cell immunity using a well-characterized mouse model of viral infection and latency. We hypothesize that the antiviral CDS T cell response hierarchy changes over time due to persistent stimulatory signals from latently-infected cells. To test this hypothesis, the first aim of this proposal will analyze the CDS T cell repertoire at various times after murine gamma-herpesvirus-68 infection to assess the functionality, activation status, and changes in the hierarchy of antiviral CDS T cells. By understanding the composition of the antiviral immune response, we may be able to identify specific viral epitopes with which to target therapeutic vaccination strategies. Latently-infected cells and cells undergoing viral reactivation from latency could present disparate viral antigens to circulating CDS T cells. In the second aim of this proposal, we will examine the CDS T cell hierarchy in the absence of viral latency or reactivation by utilizing infections with recombinant viruses that either cannot reactivate from or establish latency. The results of this aim will provide us essential insight into the regulation of the immune response in the face of an ongoing persistent infection, and may lead us to unique prophylactic vaccine strategies. PUBLIC HEALTH RELEVANCE: It is imperative to understand the interactions between the host immune response and latent viral pathogens if effective preventative or therapeutic vaccinations are to be developed. Results from these studies will have important implications in the design of vaccines that elicit the host CDS T cell response to prevent viral reactivations from latency.

描述（由申请人提供）：全球大多数人持续感染潜伏病毒。这些病毒可以在任何时候从潜伏期重新激活，导致宿主一生中的复发性疾病。目前尚不清楚宿主免疫应答如何与潜伏病毒相互作用以防止再活化，同时防止由于过度活跃的免疫引起的病理。本研究提案的目标是使用病毒感染和潜伏的良好表征的小鼠模型来确定病毒潜伏和再活化在调节抗病毒CDS T细胞免疫的产生和维持中的贡献。我们假设，抗病毒CDS T细胞反应层次随着时间的推移而变化，这是由于来自潜伏感染细胞的持续刺激信号。为了验证这一假设，本提案的第一个目的是分析鼠γ-疱疹病毒-68感染后不同时间的CDS T细胞库，以评估抗病毒CDS T细胞的功能、活化状态和层次结构的变化。通过了解抗病毒免疫反应的组成，我们或许能够识别特定的病毒表位，从而针对治疗性疫苗接种策略。潜伏感染的细胞和从潜伏期经历病毒重新激活的细胞可以向循环CDS T细胞呈现不同的病毒抗原。在该提议的第二个目的中，我们将通过利用不能从潜伏期重新激活或建立潜伏期的重组病毒感染，在没有病毒潜伏期或重新激活的情况下检查CDS T细胞层次。这一目标的结果将为我们提供必要的洞察力，在面对持续的持续感染的免疫反应的调节，并可能导致我们独特的预防性疫苗策略。公共卫生相关性：如果要开发有效的预防性或治疗性疫苗，必须了解宿主免疫应答和潜伏病毒病原体之间的相互作用。这些研究的结果将在设计疫苗中具有重要意义，这些疫苗引发宿主CDS T细胞应答以防止潜伏期的病毒再激活。