Molecular biology and spill-over potential of bat influenza A-like viruses
蝙蝠甲型流感样病毒的分子生物学和溢出潜力
基本信息
- 批准号:285723639
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2016
- 资助国家:德国
- 起止时间:2015-12-31 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The previous understanding of the influenza A virus (IAV) host range and diversity has recently been challenged by the discovery of two novel influenza subtypes in Central and South American bat species, provisionally designated H17N10 and H18N11. The surface glycoproteins of both subtypes lack the canonical receptor-binding and receptor-destroying activities of conventional hemagglutinin (HA) and neuramindase (NA) proteins, respectively.Virus isolation from infected bats or generation of recombinant viruses failed, impeding studies of their pathogenicity and zoonotic potential. We could show that bat chimeric viruses encoding HA and NA of conventional IAV fail to reassort with conventional IAV. In the first funding period, we identified the underlying mechanisms for this reassortment incompatibility, which is caused by highly conserved amino acids in the nucleoprotein (NP) of bat IAV. We were also able to generate recombinant bat IAV of both subtypes by reverse genetics after identifying highly susceptible cell lines that allowed the efficient propagation of these viruses. Furthermore, we discovered MHCII as an entry receptor for H18- and H17-mediated cell entry and could show that MHCII molecules from various bat and other species, including swine and humans, mediate cell entry. Finally, we observed that H18N11 viruses infect and replicate in various species, including mice, ferrets and bats. However, especially in mice, viral growth is associated with a deletion of the N11 head domain. In conclusion, we want to address now the following major open questions: (a) Are other cellular factors besides MHCII required for H18-mediated cell entry and endosomal release, (b) what is the function of the atypical bat flu NA-protein, (c) what is the potential of bat IAV to infect other species, and (d) are bat IAV controlled by host restriction factors of the innate immune such as MxA? With these important studies we will be able to answer the new questions from our very successful first funding period. We want to shed light onto the molecular biology of these newly discovered bat influenza viruses and also estimate their spill-over potential.
最近在中美洲和南美洲蝙蝠物种中发现了两个新的流感亚型,暂时命名为H17N10和H18N11,这对以前对甲型流感病毒(IAV)宿主范围和多样性的理解提出了挑战。这两个亚型的表面糖蛋白分别缺乏常规血凝素(HA)和神经氨基转移酶(NA)蛋白的典型受体结合和受体破坏活性。从感染蝙蝠中分离病毒或产生重组病毒失败,阻碍了对其致病性和人畜共患病潜力的研究。我们可以证明编码传统IAV的HA和NA的BAT嵌合病毒不能与传统的IAV重排。在第一个资助期,我们确定了这种重组不亲和性的潜在机制,这是由BAT IAV核蛋白(NP)中高度保守的氨基酸引起的。我们还能够通过反向遗传学产生两种亚型的重组BAT IAV,在鉴定了允许这些病毒有效繁殖的高度敏感的细胞系后。此外,我们发现MHCII是H18和H17介导的细胞进入的进入受体,并可能表明来自各种蝙蝠和其他物种(包括猪和人)的MHCII分子介导细胞进入。最后,我们观察到H18N11病毒在各种物种中感染和复制,包括老鼠、雪貂和蝙蝠。然而,尤其是在小鼠中,病毒的增长与N11头部结构域的缺失有关。总而言之,我们现在想要解决以下主要的悬而未决的问题:(A)H18介导的细胞进入和内体释放是否需要除MHCII之外的其他细胞因子;(B)非典型蝙蝠流感NA蛋白的功能是什么;(C)BAT IAV感染其他物种的可能性是什么;以及(D)BAT IAV是否受先天性免疫的宿主限制因子(如MxA)控制?有了这些重要的研究,我们将能够回答我们非常成功的第一个资助期提出的新问题。我们希望阐明这些新发现的蝙蝠流感病毒的分子生物学,并估计它们的溢出潜力。
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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Professor Dr. Martin Beer其他文献
Professor Dr. Martin Beer的其他文献
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{{ truncateString('Professor Dr. Martin Beer', 18)}}的其他基金
Recoding the SARS-CoV-2 genome - A multidisciplinary approach to generate live-attenuated coronavirus vaccines
重新编码 SARS-CoV-2 基因组 - 生产减毒冠状病毒疫苗的多学科方法
- 批准号:
453012513 - 财政年份:2020
- 资助金额:
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Bat influenza virus chimeras as basis for the development of a new type of vaccine backbone
蝙蝠流感病毒嵌合体作为开发新型疫苗骨干的基础
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276015909 - 财政年份:2015
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Out of the reservoir: identification and characterization of viral and host factors governing the pathobiology of zoonotic cowpox viruses
走出储存库:控制人畜共患牛痘病毒病理学的病毒和宿主因素的识别和表征
- 批准号:
226372197 - 财政年份:2013
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