CYTOTOXIC T CELL RESPONSES TO HHV8

HHV8 的细胞毒性 T 细胞反应

基本信息

项目摘要

Human herpesvirus type 8 (HHV-8) is a gamma family herpesvirus discovered in 1994 by Chang and Moore. The virus has been strongly implicated by serologic antibody studies and PCR detection as the etiologic agent of Kaposi's sarcoma (KS) as well as multicentric Castleman's disease and body cavity lymphomas. Based on the well-documented role of T cell immune responses in herpesvirus infections, we hypothesize that T cell immunity is induced by HHV-8 infection. We postulate further that cytotoxic T lymphocyte (CTL) activity specific for the virus is central to control of HHV-8 infection, and failure of this surveillance mechanism results in development of HHV-8 related disease. Knowledge regarding CTL responses to HHV-8 may be important in development of adequate treatment and prevention methods for this agent. Therefore, we propose the following specific aims for this project: (1) Characterize the longitudinal T cell immmunologic responses (by lytic activity, gamma interferon producing cells and tetramer staining) to regulatory, structural and latent proteins of HHV-8 during primary infection of normal adults subjects, including T cell phenotype, HLA restriction and peptide epitope mapping; (2) Define the role of the anti-HHV-8CTL response in the development of KS in HIV-1 infected subjects; (3) Determine the CTL response in situ to viral proteins related to lytic, latent and transforming properties of HHV-8, and determine if KS tumor cells are capable of suppressing CTL activity; and (4) Determine if the transforming protein K1 elicits HHV-8 clade- specific CTL responses. Application of these methodologies in our laboratories for assessing cellular immunity and HHV-8 expression, combined with access to a longitudinal cohort of HHV-8 seroconvertors in the Multicenter AIDS Cohort Study, offers a unique opportunity to advance our understanding of anti-HHV-8 CTL responses in primary infection and development of KS. Such information is also important for understanding the immune correlates of protection against HHV-8 infection as the basis for development of therapeutic regimens and prophylatic vaccines
人类8型疱疹病毒(HHV-8)是由Chang和Moore于1994年发现的一种伽玛家族疱疹病毒。血清学抗体研究和PCR检测强烈暗示该病毒是卡波西肉瘤(KS)以及多中心Castleman病和体腔淋巴瘤的病原。基于T细胞免疫反应在疱疹病毒感染中的作用,我们假设T细胞免疫是由HHV-8感染诱导的。我们进一步假设,病毒特异性的细胞毒性T淋巴细胞(CTL)活性是控制HHV-8感染的核心,这种监测机制的失败导致HHV-8相关疾病的发展。了解CTL对HHV-8的反应可能对开发适当的治疗和预防方法很重要。因此,我们提出了以下具体目标:(1)通过裂解活性,γ干扰素产生细胞和四聚体染色,表征正常成人原发性感染期间对HHV-8调节蛋白,结构蛋白和潜伏蛋白的纵向T细胞免疫反应,包括T细胞表型,HLA限制和肽表位定位;(2)明确抗hhv - 8ctl反应在HIV-1感染者KS发生中的作用;(3)确定CTL对HHV-8裂解、潜伏和转化相关病毒蛋白的原位反应,确定KS肿瘤细胞是否具有抑制CTL活性的能力;(4)确定转化蛋白K1是否引发HHV-8分支特异性CTL反应。将这些方法应用于我们的实验室来评估细胞免疫和HHV-8表达,并结合多中心艾滋病队列研究中HHV-8血清转化者的纵向队列,为我们提供了一个独特的机会,以促进我们对原发性感染和KS发展中的抗HHV-8 CTL反应的理解。这些信息对于了解预防HHV-8感染的免疫相关性也很重要,可以作为开发治疗方案和预防性疫苗的基础

项目成果

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CHARLES R RINALDO其他文献

CHARLES R RINALDO的其他文献

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{{ truncateString('CHARLES R RINALDO', 18)}}的其他基金

Cholesterol-dependent control of HIV progression by antigen presenting cells
抗原呈递细胞对 HIV 进展的胆固醇依赖性控制
  • 批准号:
    8991481
  • 财政年份:
    2015
  • 资助金额:
    $ 7.42万
  • 项目类别:
Cholesterol-dependent control of HIV progression by antigen presenting cells
抗原呈递细胞对 HIV 进展的胆固醇依赖性控制
  • 批准号:
    8921604
  • 财政年份:
    2015
  • 资助金额:
    $ 7.42万
  • 项目类别:
Dendritic Cell Core
树突状细胞核心
  • 批准号:
    8091775
  • 财政年份:
    2010
  • 资助金额:
    $ 7.42万
  • 项目类别:
Immunotherapy with Autologous HIV-Loaded Dendritic Cells
使用携带 HIV 的自体树突状细胞进行免疫治疗
  • 批准号:
    8091773
  • 财政年份:
    2010
  • 资助金额:
    $ 7.42万
  • 项目类别:
Multicenter AIDS Cohort Study
多中心艾滋病队列研究
  • 批准号:
    8145356
  • 财政年份:
    2010
  • 资助金额:
    $ 7.42万
  • 项目类别:
Multicenter AIDS Cohort Study
多中心艾滋病队列研究
  • 批准号:
    8066500
  • 财政年份:
    2010
  • 资助金额:
    $ 7.42万
  • 项目类别:
Multicenter AIDS Cohort Study
多中心艾滋病队列研究
  • 批准号:
    7919064
  • 财政年份:
    2009
  • 资助金额:
    $ 7.42万
  • 项目类别:
Multicenter AIDS Cohort Study
多中心艾滋病队列研究
  • 批准号:
    7926415
  • 财政年份:
    2009
  • 资助金额:
    $ 7.42万
  • 项目类别:
Multicenter AIDS Cohort Study
多中心艾滋病队列研究
  • 批准号:
    7926541
  • 财政年份:
    2009
  • 资助金额:
    $ 7.42万
  • 项目类别:
CELL MEDIATED IMMUNITY TO HIV, HCV KSHV INFECTIONS
针对 HIV、HCV KSHV 感染的细胞介导免疫
  • 批准号:
    7201126
  • 财政年份:
    2005
  • 资助金额:
    $ 7.42万
  • 项目类别:

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“HIV-1 抑制患者中卡波西肉瘤的血浆和细胞免疫生物标志物”
  • 批准号:
    10871931
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Anti-nucleolin aptamer AS1411: Applications in Kaposi's Sarcoma Associated Herpes Virus (KSHV) biology
抗核仁素适体 AS1411:在卡波西肉瘤相关疱疹病毒 (KSHV) 生物学中的应用
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    10619191
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    2023
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    $ 7.42万
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Project 3 - Characterizing the Amplification Factories of Epstein-Barr Virus and Kaposi's Sarcoma-associated Herpesvirus
项目 3 - 描述 Epstein-Barr 病毒和卡波西肉瘤相关疱疹病毒的扩增工厂
  • 批准号:
    10910337
  • 财政年份:
    2023
  • 资助金额:
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Rapid Sample-to-Answer Diagnosis of Kaposi's Sarcoma Across Sub-Saharan Africa using KS-COMPLETE
使用 KS-COMPLETE 对撒哈拉以南非洲地区的卡波西肉瘤进行快速样本到答案诊断
  • 批准号:
    10416778
  • 财政年份:
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The Kaposi's sarcoma-associated herpesvirus (KSHV) kaposin locus promotes latency establishment after primary infection
卡波西肉瘤相关疱疹病毒(KSHV)卡波辛基因座促进初次感染后潜伏期的建立
  • 批准号:
    463159
  • 财政年份:
    2022
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    $ 7.42万
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    Operating Grants
Rapid Sample-to-Answer Diagnosis of Kaposi's Sarcoma Across Sub-Saharan Africa using KS-COMPLETE
使用 KS-COMPLETE 对撒哈拉以南非洲地区的卡波西肉瘤进行快速样本到答案诊断
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Determining how Kaposi's sarcoma-associated herpesvirus hijacks caspase function to inhibit anti-viral responses
确定卡波西肉瘤相关疱疹病毒如何劫持半胱天冬酶功能以抑制抗病毒反应
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    10403006
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    2021
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    $ 7.42万
  • 项目类别:
KSHV-induced oncogenic changes in a primary human lymphatic endothelial cell model of Kaposi's Sarcoma
KSHV 诱导的卡波西肉瘤原代人淋巴内皮细胞模型的致癌变化
  • 批准号:
    10327223
  • 财政年份:
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卡波西肉瘤相关疱疹病毒-宿主混合复合物的组成分析及药物靶点的发现
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    21K08509
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    2021
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    $ 7.42万
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KSHV-induced oncogenic changes in a primary human lymphatic endothelial cell model of Kaposi's Sarcoma
KSHV 诱导的卡波西肉瘤原代人淋巴内皮细胞模型的致癌变化
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    10457488
  • 财政年份:
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