Assembly of Live Nipah Virus with Complement Factors

活尼帕病毒与补体因子的组装

基本信息

项目摘要

DESCRIPTION (provided by applicant): The complement system is a critical part of innate immune responses that most animal viruses encounter during natural infections. While it is clear that complement (C') is an important factor in neutralization of some RNA viruses, very few mechanistic details are known about how C' regulates paramyxovirus infections. Here, we seek to fill gaps in understanding of interactions of complement (C') with the emerging highly pathogenic paramyxovirus Nipah virus (NiV). This project emerged from our recent published finding that: 1) complement is activated in vitro by pseudotypes containing the NiV F and G glycoproteins, but importantly, unlike any other paramyxovirus we have tested so far this does not result in neutralization. Our preliminary data also demonstrate that: 2) the cellular C' inhibior Factor I protease associates with the NiV F but not HN protein and 3) Factor I associated with NiV pseudotypes can inactivate C3b by cleavage into iC3b. The novelty of the second and third U findings is that no other pathogen has been reported so far to recruit Factor I as a mechanism to evade complement. In addition, support for our hypothesis would show a new function for the paramyxovirus F U U protein in evading innate immunity. U In Aim 1, we will use biochemical approaches to test the hypothesis that functional human Factor I U U interacts specifically with the NiV F protein. Work in Aim 2 will involve studies with live NiV infection under U U Biosafety Level 4 (BSL4) conditions. We will determine the extent to which live NiV activates C' in vitro and the capacity of C' to neutralize NiV infectivity. In addition to recruitment of soluble Factor , we hypothesize that NiV also captures cell surface inhibitors of C' such as CD46 and CD55. This will be tested using live NiV infection of tissue culture cells that express varying levels of inhibitors. This pilot project seeks to extend our novel findings from studies with NiV pseudotypes into live NiV under BSL-4 conditions, and to gain further supporting data for a novel mechanism of C' evasion. Both are necessary steps to establish a secure foundation for more mechanistic detailed studies with live virus and into experiments in animal models.
说明(申请人提供):补体系统是大多数动物病毒在自然感染过程中遇到的先天免疫反应的关键部分。虽然补体(C‘)显然是一些RNA病毒中和的一个重要因素,但关于C’如何调节副粘病毒感染的机制细节知之甚少。在这里,我们试图填补补体(C‘)与新出现的高致病性副粘病毒尼帕病毒(Niv)相互作用的理解空白。这个项目源于我们最近发表的发现:1)补体在体外被含有Niv F和G糖蛋白的伪型激活,但重要的是,与我们迄今测试的任何其他副粘病毒不同,这不会导致中和。我们的初步数据还表明:2)细胞内的C‘抑制因子I酶与NIV F结合,而不与HN蛋白结合;3)与NIV伪型相关的因子I可以通过裂解iC3b来灭活C3b。第二个和第三个U发现的新奇之处在于,到目前为止还没有其他病原体报道招募凝血因子I作为逃避补体的机制。此外,支持我们的假设将显示副粘病毒F U U蛋白在逃避天然免疫中的新功能。U在目标1中,我们将使用生化方法来验证功能性人类因子I U U与Niv F蛋白特异性相互作用的假设。目标2的工作将涉及在U U生物安全级别4(BSL4)条件下对活的新城疫病毒感染的研究。我们将测定活的新城疫病毒在体外激活C‘的程度以及C’中和新城疫病毒感染性的能力。除了可溶性因子的募集,我们推测NIV还捕获了C‘的细胞表面抑制物,如CD46和CD55。这将通过组织培养细胞的活Niv感染进行测试,组织培养细胞表达不同水平的 抑制剂。这个试点项目试图将我们从NIV伪型研究中得到的新发现推广到BSL-4条件下的活体NIV,并为C‘逃避的新机制获得进一步的支持数据。这两个步骤都是为更机械化的活体病毒详细研究和动物模型实验奠定安全基础的必要步骤。

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 }}

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

{{ 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('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:
    $ 5.85万
  • 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:
    $ 5.85万
  • 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:
    $ 5.85万
  • 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:
    $ 5.85万
  • 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:
    $ 5.85万
  • 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:
    $ 5.85万
  • 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:
    $ 5.85万
  • 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:
    $ 5.85万
  • 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:
    $ 5.85万
  • 项目类别:
Complement-mediated Neutralization of Mumps Virus and SV5
补体介导的腮腺炎病毒和 SV5 的中和
  • 批准号:
    8069009
  • 财政年份:
    2010
  • 资助金额:
    $ 5.85万
  • 项目类别:

相似海外基金

Study for interspecies transmission of animal viruses using metagenomics approach
利用宏基因组学方法研究动物病毒的种间传播
  • 批准号:
    18K05977
  • 财政年份:
    2018
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular biology of plant and animal viruses: plant viruses as gene vectors for transient expression of foreign proteins in plants
植物和动物病毒的分子生物学:植物病毒作为基因载体在植物中瞬时表达外源蛋白
  • 批准号:
    6706-1997
  • 财政年份:
    1997
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Discovery Grants Program - Individual
Molecular biology of plant and animal viruses: mechanisms of resistance and gene expression
动植物病毒的分子生物学:抗性机制和基因表达
  • 批准号:
    6706-1993
  • 财政年份:
    1996
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Discovery Grants Program - Individual
Molecular biology of plant and animal viruses: mechanisms of resistance and gene expression
动植物病毒的分子生物学:抗性机制和基因表达
  • 批准号:
    6706-1993
  • 财政年份:
    1995
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Discovery Grants Program - Individual
Molecular biology of plant and animal viruses: mechanisms of resistance and gene expression
动植物病毒的分子生物学:抗性机制和基因表达
  • 批准号:
    6706-1993
  • 财政年份:
    1994
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Discovery Grants Program - Individual
Studies on the mechanisms of persistent infection and reactivation of animal viruses.
动物病毒持续感染和再激活机制研究。
  • 批准号:
    06404015
  • 财政年份:
    1994
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Molecular biology of plant and animal viruses: mechanisms of resistance and gene expression
动植物病毒的分子生物学:抗性机制和基因表达
  • 批准号:
    6706-1993
  • 财政年份:
    1993
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Discovery Grants Program - Individual
Studies on the mechanisms of persistent infection and reactivation of animal viruses
动物病毒持续感染和再激活机制研究
  • 批准号:
    03404014
  • 财政年份:
    1991
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (A)
Virology-Immunology Course Considers Animal Viruses
病毒学-免疫学课程考虑动物病毒
  • 批准号:
    9151450
  • 财政年份:
    1991
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Standard Grant
Assembly and Dissassembly of Animal Viruses
动物病毒的组装和拆卸
  • 批准号:
    8701605
  • 财政年份:
    1987
  • 资助金额:
    $ 5.85万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了