Gammaherpesvirus and IL-17: using host antibacterial defense to benefit chronic virus infection
伽玛疱疹病毒和 IL-17:利用宿主抗菌防御来有益于慢性病毒感染
基本信息
- 批准号:10283264
- 负责人:
- 金额:$ 21.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAnatomyAnti-Bacterial AgentsAntibodiesApplications GrantsAutomobile DrivingB cell differentiationB-Cell LymphomasB-LymphocytesBacteriaBacterial InfectionsCellsChronicDevelopmentHomologous GeneHumanHuman Herpesvirus 4Human Herpesvirus 8Immunoglobulin Somatic HypermutationInfectionInterleukin-17LifeLife Cycle StagesLymphomaLymphomagenesisMalignant NeoplasmsMemoryMemory B-LymphocyteModelingMusMycosesPathogenicityPhenotypePlasmaPopulationPredispositionProcessProliferatingRiskRisk FactorsRoleSaimiriine Herpesvirus 2Signal TransductionStructure of germinal center of lymph nodeTestingTimeViralViral reservoirVirusVirus DiseasesVirus Latencyantimicrobialbacterial geneticsbasechronic infectionco-infectioncytokinegammaherpesvirusinsightlatent infectionnovelnovel strategiespathogenic bacteriapathogenic fungusresponse
项目摘要
Abstract
Gammaherpesviruses establish infection in >95% of adults and are associated with multiple cancers, including
B cell lymphomas. These viruses usurp B cell differentiation by infecting naïve B cells and driving entry of
latently infected and bystander B cells into a germinal center response to ultimately achieve life-long latency in
memory B cells. Importantly, the germinal center response is highly mutagenic and is thought to be the target
of viral transformation. The mechanisms by which gammaherpesviruses usurp B cell differentiation, including
germinal center response, are largely unknown. This proposal is based on our discovery that IL-17A
selectively promotes the gammaherpesvirus-driven germinal center response and viral reactivation, two
processes that are associated with increased risk of viral lymphomagenesis. IL-17A is induced by and
contributes to the clearance of bacterial and fungal pathogens, with our studies revealing an unexpected
proviral role of this cytokine. The proposed studies test the hypothesis that natural induction of IL-17A by
bacterial pathogens is usurped by gammaherpesviruses to promote germinal center response and
viral reactivation. The proposed studies will determine the extent to which a systemic or anatomically
restricted bacterial infection impacts gammaherpesvirus-driven germinal center response and viral reactivation
and use host and bacterial genetics to define the role of IL-17A in this process. Successful completion of the
proposed studies will for the first time define the impact of natural IL-17A induction by common bacterial
pathogens on the key pathogenic processes associated with viral lymphomagenesis and will provide insight
into novel approaches to target susceptibility to virus-driven lymphomas.
摘要
伽马疱疹病毒可导致95%的成年人感染,并与多种癌症有关,包括
B细胞淋巴瘤。这些病毒通过感染幼稚的B细胞并驱动
潜伏感染和旁观者B细胞进入生发中心反应,最终实现终生潜伏期
记忆B细胞。重要的是,生发中心的反应是高度诱变的,被认为是目标。
病毒转化的可能性。伽马疱疹病毒侵占B细胞分化的机制包括
生发中心的反应,很大程度上是未知的。这一建议是基于我们的发现,IL-17A
选择性地促进伽马疱疹病毒驱动的生发中心反应和病毒重新激活,两个
与病毒淋巴增生症风险增加相关的过程。IL-17A是由和诱导的
有助于清除细菌和真菌病原体,我们的研究揭示了一种意想不到的
这种细胞因子的前驱作用。拟议的研究验证了这样的假设,即自然诱导的IL-17A是通过
细菌病原体被伽马疱疹病毒取代,以促进生发中心反应和
病毒重新激活。拟议的研究将确定系统性或解剖学上的
限制性细菌感染对伽马疱疹病毒驱动的生发中心反应和病毒再激活的影响
并利用宿主和细菌遗传学来确定IL-17A在这一过程中的作用。圆满完成
拟议的研究将首次确定由普通细菌诱导的自然IL-17A的影响
病原体与病毒淋巴增生症相关的关键致病过程,并将提供洞察力
针对病毒驱动的淋巴瘤易感性的新方法。
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)
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Vera L. Tarakanova其他文献
34 - Nitric Oxide Prevents Pancreatic P-Cell Apoptosis Via Inhibition of the DNA Damage Response
- DOI:
10.1016/j.freeradbiomed.2015.10.071 - 发表时间:
2015-10-01 - 期刊:
- 影响因子:
- 作者:
Bryndon J. Oleson;Katarzyna A. Broniowska;Aaron Naatz;Vera L. Tarakanova;John A. Corbett - 通讯作者:
John A. Corbett
Vera L. Tarakanova的其他文献
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{{ truncateString('Vera L. Tarakanova', 18)}}的其他基金
Gammaherpesvirus protein kinase: a master manipulator of the host during chronic infection.
伽玛疱疹病毒蛋白激酶:慢性感染期间宿主的主要操纵者。
- 批准号:
10518464 - 财政年份:2022
- 资助金额:
$ 21.41万 - 项目类别:
Gammaherpesvirus protein kinase: a master manipulator of the host during chronic infection.
伽玛疱疹病毒蛋白激酶:慢性感染期间宿主的主要操纵者。
- 批准号:
10651854 - 财政年份:2022
- 资助金额:
$ 21.41万 - 项目类别:
Gammaherpesvirus and IL-17: using host antibacterial defense to benefit chronic virus infection
伽玛疱疹病毒和 IL-17:利用宿主抗菌防御来有益于慢性病毒感染
- 批准号:
10470873 - 财政年份:2021
- 资助金额:
$ 21.41万 - 项目类别:
IRF-1: a brake to limit gammaherpesvirus infection and pathogenesis
IRF-1:限制伽马疱疹病毒感染和发病机制的刹车
- 批准号:
10066315 - 财政年份:2016
- 资助金额:
$ 21.41万 - 项目类别:
ATM and gammaherpesvirus infection: a precarious balance
ATM 和伽玛疱疹病毒感染:不稳定的平衡
- 批准号:
9278127 - 财政年份:2014
- 资助金额:
$ 21.41万 - 项目类别:
ATM and gammaherpesvirus infection: a precarious balance
ATM 和伽玛疱疹病毒感染:不稳定的平衡
- 批准号:
9064721 - 财政年份:2014
- 资助金额:
$ 21.41万 - 项目类别:
ATM and gammaherpesvirus infection: a precarious balance
ATM 和伽玛疱疹病毒感染:不稳定的平衡
- 批准号:
8789294 - 财政年份:2014
- 资助金额:
$ 21.41万 - 项目类别:
The role of gammaherpesvirus protein kinase in lytic and latent infection
伽马疱疹病毒蛋白激酶在溶解性和潜伏性感染中的作用
- 批准号:
8132757 - 财政年份:2010
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$ 21.41万 - 项目类别:
Regulation of gHV68-induced B cell proliferation
gHV68 诱导的 B 细胞增殖的调节
- 批准号:
6936276 - 财政年份:2005
- 资助金额:
$ 21.41万 - 项目类别:
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