Complement-mediated Neutralization of Mumps Virus and SV5
补体介导的腮腺炎病毒和 SV5 的中和
基本信息
- 批准号:7570466
- 负责人:
- 金额:$ 19.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-01-01 至 2010-12-31
- 项目状态:已结题
- 来源:
- 关键词:Blocking AntibodiesBypassCellsComplementComplement ActivationCytolysisDataEpithelial CellsGlycoproteinsGoalsHumanImmune systemInfectionMapsMediatingMumps virusOutcomeParamyxovirusPathway interactionsPopulationProductionProteinsRNA InterferenceRecording of previous eventsRefractoryResearchResistanceRoleSignal TransductionSimian virus 5SurfaceSystemTestingUp-RegulationVaccinationViralVirionVirusVirus-like particleWorkbasebonecomplement pathwayflexibilityinnovationinterestmutantnovelnovel therapeuticsnovel virusparticlepreventpublic health relevanceresearch study
项目摘要
DESCRIPTION (provided by applicant): This proposal is based on two remarkable findings from our lab. First, complement neutralizes the closely related paramyxoviruses Simian Virus 5 (SV5) and Mumps Virus (MuV), but by distinct mechanisms involving formation of massive SV5 aggregates versus complement mediated lysis of MuV particles. Secondly, our microarray data indicate that infection with the noncytopathic WT SV5 results in elevated levels of host cell regulators of complement and these virus-infected cells are not lysed by complement. Our long term goal of this project is to understand the cellular and viral factors that dictate the outcome of interactions of paramyxoviruses with complement. The short term goals are to 1) utilize a novel experimental system to identify viral signals that dictate the extent and pathway of complement neutralization and to 2) define the role of SV5-induced regulators of complement in preventing lysis of virus infected cells. An innovative aspect of our application is the use of SV5 and MuV virus-like particles (VLP) to analyze virus:complement interactions. This is a powerful and flexible system, in that novel VLPs that differ in viral components can be produced when these alterations would otherwise not be tolerated in the context of a bone fide infectious virus. In Aim 1, we will identify the cellular pathways and viral determinants involved in interactions of complement with SV5 and MuV virus-like particles (VLPs). The complement pathways and the viral determinants of complement activation will be identified through the use of VLPs that differ in their content of viral glycoproteins HN, F and SH. In Aim 2, we will test the hypothesis that SV5-infected epithelial cells are resistant to complement-mediate lysis due to upregulation of host cell regulators of complement. There is intense interest in defining mechanisms that modulate the interplay between viruses and the host innate immune system, but the role of complement in neutralization of paramyxoviruses is not completely understood. Our studies have important implications for understanding complement-mediated neutralization of viruses, the re-emergence in the human population of paramyxoviruses such MuV, and persistent infections, as well as great potential for exploiting the new information for novel therapeutic applications. PUBLIC HEALTH RELEVANCE: There is intense interest in defining mechanisms that modulate the interplay between viruses and the host innate immune system, but the role of complement in neutralization of paramyxoviruses is not completely understood. Our work will have important implications for control of viruses such as MuV, which has re-emerged despite wide-spread vaccination. In addition, our work with virus-induced inhibition of complement has implication for mechanisms by which viruses establish persistent infections that are refractory to recognition by host immune systems.
描述(由申请人提供):本提案基于我们实验室的两项显著发现。首先,补体中和密切相关的副粘病毒猿猴病毒5(SV 5)和腮腺炎病毒(MuV),但通过涉及大量SV 5聚集体的形成与补体介导的MuV颗粒裂解的不同机制。其次,我们的微阵列数据表明,感染非致细胞病变的WT SV 5导致补体的宿主细胞调节因子水平升高,并且这些病毒感染的细胞不被补体裂解。我们这个项目的长期目标是了解决定副粘病毒与补体相互作用结果的细胞和病毒因素。短期目标是:1)利用新的实验系统来鉴定决定补体中和程度和途径的病毒信号; 2)确定SV 5诱导的补体调节因子在预防病毒感染细胞裂解中的作用。我们应用的一个创新方面是使用SV 5和MuV病毒样颗粒(VLP)来分析病毒:补体相互作用。这是一个强大而灵活的系统,因为当这些改变在真正的感染性病毒的情况下不被容忍时,可以产生病毒组分不同的新型VLP。在目标1中,我们将确定参与补体与SV 5和MuV病毒样颗粒(VLP)相互作用的细胞途径和病毒决定簇。将通过使用病毒糖蛋白HN、F和SH含量不同的VLP来鉴定补体途径和补体激活的病毒决定簇。在目标2中,我们将检验以下假设:由于补体的宿主细胞调节因子的上调,SV 5感染的上皮细胞对补体介导的裂解具有抗性。人们对确定调节病毒与宿主先天免疫系统之间相互作用的机制非常感兴趣,但补体在中和副粘病毒中的作用尚未完全了解。我们的研究对于理解补体介导的病毒中和、副粘病毒(如MuV)在人群中的重新出现和持续性感染具有重要意义,并且对于开发新的治疗应用的新信息具有巨大潜力。公共卫生相关性:人们对确定调节病毒与宿主先天免疫系统之间相互作用的机制非常感兴趣,但补体在中和副粘病毒中的作用尚未完全了解。我们的工作将对MuV等病毒的控制产生重要影响,尽管广泛接种疫苗,但MuV病毒已经重新出现。此外,我们对病毒诱导的补体抑制的研究对病毒建立难以被宿主免疫系统识别的持续性感染的机制具有意义。
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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Griffith D. Parks其他文献
Complement evasion by vesicular stomatitis virus involves recruitment of host complement regulatory proteins
- DOI:
10.1016/j.molimm.2010.05.129 - 发表时间:
2010-08-01 - 期刊:
- 影响因子:
- 作者:
John B. Johnson;Douglas S. Lyles;Griffith D. Parks - 通讯作者:
Griffith D. Parks
Griffith D. Parks的其他文献
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{{ truncateString('Griffith D. Parks', 18)}}的其他基金
Complement Resistance Acquired During Acute to Persistent Rubulavirus Infection
急性至持续性风疹病毒感染期间获得的补体耐药性
- 批准号:
10645486 - 财政年份:2023
- 资助金额:
$ 19.68万 - 项目类别:
Assembly of Live Nipah Virus with Complement Factors
活尼帕病毒与补体因子的组装
- 批准号:
8896985 - 财政年份:2012
- 资助金额:
$ 19.68万 - 项目类别:
Assembly of Live Nipah Virus with Complement Factors
活尼帕病毒与补体因子的组装
- 批准号:
8470128 - 财政年份:2012
- 资助金额:
$ 19.68万 - 项目类别:
Assembly of Live Nipah Virus with Complement Factors
活尼帕病毒与补体因子的组装
- 批准号:
8358727 - 财政年份:2012
- 资助金额:
$ 19.68万 - 项目类别:
Paramyxovirus Activation and Inhibition of Complement Pathways
副粘病毒激活和补体途径的抑制
- 批准号:
8286153 - 财政年份:2011
- 资助金额:
$ 19.68万 - 项目类别:
Paramyxovirus Activation and Inhibition of Complement Pathways
副粘病毒激活和补体途径的抑制
- 批准号:
8897063 - 财政年份:2011
- 资助金额:
$ 19.68万 - 项目类别:
Paramyxovirus Activation and Inhibition of Complement Pathways
副粘病毒激活和补体途径的抑制
- 批准号:
8469683 - 财政年份:2011
- 资助金额:
$ 19.68万 - 项目类别:
Paramyxovirus Activation and Inhibition of Complement Pathways
副粘病毒激活和补体途径的抑制
- 批准号:
8848749 - 财政年份:2011
- 资助金额:
$ 19.68万 - 项目类别:
Paramyxovirus Activation and Inhibition of Complement Pathways
副粘病毒激活和补体途径的抑制
- 批准号:
8660023 - 财政年份:2011
- 资助金额:
$ 19.68万 - 项目类别:
Paramyxovirus Activation and Inhibition of Complement Pathways
副粘病毒激活和补体途径的抑制
- 批准号:
8039506 - 财政年份:2011
- 资助金额:
$ 19.68万 - 项目类别:
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