Role of gammaHV68 M1 antigen in Vbeta4+ T cell expansion and fibrosis

gammaHV68 M1 抗原在 Vbeta4 T 细胞扩增和纤维化中的作用

基本信息

  • 批准号:
    7387671
  • 负责人:
  • 金额:
    $ 43.14万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-01-01 至 2012-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Herpesvirus disease pathogenesis is closely linked to host immune status. Murine gammaherpesvirus 68 (?HV68) provides a model for studying the outcome of chronic gammaherpesvirus infection in the immunocompetent versus immunodeficient host. ?HV68 infection of a wild-type mouse results in a limited, acute infection at the site of inoculation, followed by latent, disseminated infection in a variety of tissues and cell types. Although wild-type mice rarely display any virus-related pathology, interferon-gamma receptor- deficient hosts (IFN?R-/-) develop potentially lethal, systemic inflammatory disease. This immune-mediated pathology consists of multi-organ fibrotic tissue damage and vasculitis, associated with chronic reactivation of latent virus and persistent replication. Interestingly, many features of this disease are absent during chronic infection with a ?HV68 mutant lacking the antigen encoded by the M1 open reading frame (ORF) - even though this mutant virus is not impaired for either acute replication or establishment of a latent infection. The M1 antigen, which bears sequence homology to some pox virus serpins (although it lacks critical catalytic residues) and to the ?HV68 secreted high affinity chemokine binding protein M3, has been shown to regulate ?HV68 reactivation from latency. The mechanism by which M1 exerts this effect, and the extent of immune system involvement, is unknown. Throughout the course of latency, the ?HV68 antiviral response is not appreciably stimulated with one notable exception - the significant expansion of V24+ CD8+ T cells. We have recently shown that expression of the M1 antigen is required for this response. This application aims to study the potentially novel mechanism(s) by which the ?HV68 M1 gene product induces V24+ T cell activity, perhaps to self-limit reactivation from latency through expression of IFN-?, and the role such T cells might play in mediating chronic disease in an immunocompromised host. The following 3 aims are proposed: Aim 1: Characterize M1 transcript structure(s) and regulation of M1 gene expression. Aim 2: Define the mechanism of M1-induced V24+ T cell activation and its influence on T cell function. Aim 3: Define the role of M1 and V24+ T cells in regulating ?HV68 reactivation, latency, and virus-induced systemic inflammatory disease.
描述(由申请人提供):疱疹病毒疾病的发病机制与宿主免疫状态密切相关。鼠γ疱疹病毒68 (?HV68)为研究免疫正常与免疫缺陷宿主慢性伽玛疱疹病毒感染的结果提供了一个模型。?野生型小鼠的HV68感染在接种部位引起有限的急性感染,随后在多种组织和细胞类型中发生潜伏性、播散性感染。尽管野生型小鼠很少表现出任何与病毒相关的病理,干扰素受体缺陷宿主(IFN?R-/-)发展为潜在致命的全身性炎症性疾病。这种免疫介导的病理包括多器官纤维化组织损伤和血管炎,与潜伏病毒的慢性再激活和持续复制有关。有趣的是,这种疾病的许多特征在慢性感染a ?HV68突变体缺乏由M1开放阅读框(ORF)编码的抗原,尽管这种突变病毒在急性复制或建立潜伏感染方面没有受损。M1抗原与某些痘病毒蛇形蛋白(尽管它缺乏关键的催化残基)和?HV68分泌高亲和力趋化因子结合蛋白M3,已被证明可调节?HV68从延迟中重新激活。M1发挥这种作用的机制以及免疫系统参与的程度尚不清楚。在整个潜伏期过程中,?HV68抗病毒反应没有明显的刺激,但有一个明显的例外- V24+ CD8+ T细胞的显著扩增。我们最近的研究表明,这种反应需要M1抗原的表达。该应用程序旨在研究潜在的新机制,通过该机制?HV68 M1基因产物诱导V24+ T细胞活性,可能通过表达IFN-?这些T细胞可能在免疫功能低下的宿主中介导慢性疾病中发挥作用。本文提出以下3个目标:目标1:表征M1转录本结构和M1基因表达调控。目的2:明确m1诱导V24+ T细胞活化的机制及其对T细胞功能的影响。目的3:明确M1和V24+ T细胞在调节?HV68再激活、潜伏期和病毒诱导的全身性炎症疾病。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

SAMUEL H SPECK其他文献

SAMUEL H SPECK的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('SAMUEL H SPECK', 18)}}的其他基金

Role of MHV68 v-cyclin in virus egress
MHV68 v-cyclin 在病毒流出中的作用
  • 批准号:
    8807186
  • 财政年份:
    2014
  • 资助金额:
    $ 43.14万
  • 项目类别:
Co-infection of mice with MHV68 and rodent Plasmodium species
小鼠同时感染 MHV68 和啮齿类疟原虫
  • 批准号:
    8285405
  • 财政年份:
    2012
  • 资助金额:
    $ 43.14万
  • 项目类别:
Co-infection of mice with MHV68 and rodent Plasmodium species
小鼠同时感染 MHV68 和啮齿类疟原虫
  • 批准号:
    8416962
  • 财政年份:
    2012
  • 资助金额:
    $ 43.14万
  • 项目类别:
Role of gammaHV68 M1 antigen in Vbeta4+ T cell expansion and fibrosis
gammaHV68 M1 抗原在 Vbeta4 T 细胞扩增和纤维化中的作用
  • 批准号:
    8010967
  • 财政年份:
    2008
  • 资助金额:
    $ 43.14万
  • 项目类别:
Role of gammaHV68 M1 antigen in Vbeta4+ T cell expansion and fibrosis
gammaHV68 M1 抗原在 Vbeta4 T 细胞扩增和纤维化中的作用
  • 批准号:
    8204743
  • 财政年份:
    2008
  • 资助金额:
    $ 43.14万
  • 项目类别:
Role of gammaHV68 M1 antigen in Vbeta4+ T cell expansion and fibrosis
gammaHV68 M1 抗原在 Vbeta4 T 细胞扩增和纤维化中的作用
  • 批准号:
    7545503
  • 财政年份:
    2008
  • 资助金额:
    $ 43.14万
  • 项目类别:
Role of gammaHV68 M1 antigen in Vbeta4+ T cell expansion and fibrosis
gammaHV68 M1 抗原在 Vbeta4 T 细胞扩增和纤维化中的作用
  • 批准号:
    7749544
  • 财政年份:
    2008
  • 资助金额:
    $ 43.14万
  • 项目类别:
FUNCTION OF THE GAMMAHV68 M2 ANTIGEN
GAMMAHV68 M2 抗原的功能
  • 批准号:
    7349211
  • 财政年份:
    2006
  • 资助金额:
    $ 43.14万
  • 项目类别:
ROLE OF B CELLS IN MURINE GAMMAHERPES -68 LATENCY
B 细胞在鼠丙型疱疹 -68 潜伏期中的作用
  • 批准号:
    7349210
  • 财政年份:
    2006
  • 资助金额:
    $ 43.14万
  • 项目类别:
REGULATION OF EBV TRANSCRIPTION IN BURKITT'S LYMPHOMA
伯基特淋巴瘤中 EBV 转录的调控
  • 批准号:
    7349162
  • 财政年份:
    2006
  • 资助金额:
    $ 43.14万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 43.14万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了