Elucidating the immune response of Schreiber's bats to Lloviu virus infection in vitro and in vivo

阐明施赖伯蝙蝠对 Lloviu 病毒感染的体外和体内免疫反应

基本信息

  • 批准号:
    10458900
  • 负责人:
  • 金额:
    $ 24.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-02-24 至 2024-01-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Bats play an important role as natural reservoirs of numerous RNA viruses with the potential to cause significant harm to humans. In this proposal, we focus on Lloviu virus (LLOV), an under-investigated filovirus that circulates in Schreiber’s bats (Miniopterus schreibersii) in Europe. Although the pathogenic potential of LLOV for humans is not known, the close relationship of LLOV to the highly pathogenic Ebola and Marburg viruses raises concerns that a potential spillover event could lead to an outbreak among humans. LLOV was first detected Schreiber’s bats in Spain in 2002 and then again in Hungary in 2016. Sequence comparison of the Spanish and the Hungarian LLOV RNA genomes suggests that RNA editing by cellular deaminases, such as ADAR and APOBEC, might play a role in LLOV sequence diversification. In this application, we propose to explore if host-mediated RNA editing drives LLOV sequence divergence and evolution in Schreiber’s bats. In Aim 1, we propose to sample Schreiber’s bats from geographically distinct colonies and obtain LLOV sequence information from infected bats for comparative analysis. We will further develop tools based on highly sensitive droplet RT-PCR and RNA FISH that allow to determine the expression pattern of ADARs and APOBECs in LLOV-infected bat cell culture and in blood samples from infected animals. In Aim 2, based on the determined ADAR and APOBEC expression patterns, we will knockout select ADAR and/or APOBEC genes that might be involved in LLOV RNA editing in the bat cell line and examine the role of these genes in LLOV sequence diversification and viral fitness in serial passaging experiments and cell culture infection studies. Upon completion of this work, we will have revealed whether host-specific RNA editors are the drivers of LLOV evolution in bat cells. This work will contribute to our understanding of host-driven viral sequence divergence and might help assess the risk of potential LLOV spillover events from bats to humans through host-driven changes in viral sequences.
摘要

项目成果

期刊论文数量(0)
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Elke C Muhlberger其他文献

Elke C Muhlberger的其他文献

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{{ truncateString('Elke C Muhlberger', 18)}}的其他基金

Elucidating the immune response of Schreiber's bats to Lloviu virus infection in vitro and in vivo
阐明施赖伯氏蝙蝠对 Lloviu 病毒感染的体外和体内免疫反应
  • 批准号:
    10579294
  • 财政年份:
    2022
  • 资助金额:
    $ 24.38万
  • 项目类别:
Filovirus replication: initiation mechanism and role of RNA secondary structures
丝状病毒复制:RNA二级结构的启动机制和作用
  • 批准号:
    8904599
  • 财政年份:
    2014
  • 资助金额:
    $ 24.38万
  • 项目类别:
Filovirus replication: initiation mechanism and role of RNA secondary structures
丝状病毒复制:RNA二级结构的启动机制和作用
  • 批准号:
    8771943
  • 财政年份:
    2014
  • 资助金额:
    $ 24.38万
  • 项目类别:
Early Host Immune Response in Protection Against Filovirus Infection
预防丝状病毒感染的早期宿主免疫反应
  • 批准号:
    8099009
  • 财政年份:
    2009
  • 资助金额:
    $ 24.38万
  • 项目类别:
Early Host Immune Response in Protection Against Filovirus Infection
预防丝状病毒感染的早期宿主免疫反应
  • 批准号:
    8474594
  • 财政年份:
    2009
  • 资助金额:
    $ 24.38万
  • 项目类别:
Early Host Immune Response in Protection Against Filovirus Infection
预防丝状病毒感染的早期宿主免疫反应
  • 批准号:
    7680508
  • 财政年份:
    2009
  • 资助金额:
    $ 24.38万
  • 项目类别:
Early Host Immune Response in Protection Against Filovirus Infection
预防丝状病毒感染的早期宿主免疫反应
  • 批准号:
    8277871
  • 财政年份:
    2009
  • 资助金额:
    $ 24.38万
  • 项目类别:
Early Host Immune Response in Protection Against Filovirus Infection
预防丝状病毒感染的早期宿主免疫反应
  • 批准号:
    7864186
  • 财政年份:
    2009
  • 资助金额:
    $ 24.38万
  • 项目类别:
Biomolecule Production Core
生物分子生产核心
  • 批准号:
    8461423
  • 财政年份:
    2006
  • 资助金额:
    $ 24.38万
  • 项目类别:
Biomolecule Production Core
生物分子生产核心
  • 批准号:
    8709527
  • 财政年份:
  • 资助金额:
    $ 24.38万
  • 项目类别:

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