Surface glycoproteins G and F of an African bat henipavirus: Functional characterization and importance for interspecies transmission

蝙蝠被认为是包括副粘病毒在内的不同病毒家族的主要宿主。高致病性副粘病毒为尼帕病毒(Nipah Virus，NIV)和亨德拉病毒(Hendra Virus)。它们的天然储藏库是流行于东南亚的翼蝙科蝙蝠。最近在非洲蝙蝠中发现了赫尼帕病毒的基因组RNA。尽管到目前为止还没有从非洲蝙蝠身上分离到传染性埃尼帕病毒，但接触过非洲蝙蝠的人已经被证明对亚洲埃尼帕病毒的抗原呈血清阳性。为了估计病毒从蝙蝠传播到人类的人畜共患病风险，有必要分离传染性病毒并分析其复制情况。为了了解这些病毒的宿主特异性和细胞嗜性，有必要分析病毒表面糖蛋白的生物学活性，这些糖蛋白通过病毒和细胞膜之间的融合事件介导附着到细胞表面和进入细胞。本项目的目的是表征非洲埃尼帕病毒M74的表面蛋白G和F在病毒融合活动中的相互作用。在初步工作中，已经表明这些蛋白质在诱导合胞体形成即多核巨细胞方面效率较低。病毒融合活性的这种损害主要是由于M74-G蛋白的表面表达效率低下。我们想要阐明导致表面运输效率低下的M74-G的结构元素。将分析M74-F蛋白与NIV-F蛋白的功能差异。除了细胞与细胞的融合外，还将分析M74表面糖蛋白是否具有介导感染的能力。为此，M74-G和M74-F蛋白将被整合到基于缺陷性水泡性口炎病毒的假病毒中。预期的结果不仅将增加我们对M74融合活性的了解，还将为我们提供从非洲蝙蝠中分离传染性埃尼帕病毒最有希望的条件。这是分析这些病毒的跨物种传播潜力，从而评估其人畜共患病风险的重要一步。

Bats are considered a major host reservoir for different virus families, including paramyxoviruses. Highly pathogenic paramyxoviruses are the henipaviruses Nipah virus (NiV) and Hendra virus. Their natural reservoir are bats of the family Pteropodidae that are prevalent in Southeast Asia. Genomic henipavirus RNA has recently been detected in African bats of the species Eidolon helvum. Though infectious henipaviruses have so far not been isolated from African bats, humans that have contact to African bats have been shown to be seropositive for antigen from Asian henipaviruses. To estimate the zoonotic risk of virus transmission from bats to humans, it is necessary to isolate infectious virus and analyze the replication. To understand the host specificity and cell tropism of these viruses it is essential to analyze the biological activities of the viral surface glycoproteins that mediate attachment to the cell surface and entry into cells by a fusion event between the viral and the cellular membrane.Aim of the project is to characterize the surface proteins G and F of the African henipavirus M74 with respect to their interaction in the viral fusion actvitiy. In preliminary work it has been shown that the proteins are less efficient in inducing the formation of syncytia, i.e multinucleated giant cells. This impairment of the viral fusion activity is mainly due to the inefficient surface expression of the M74-G protein. We want to elucidate the structural elements of M74-G that are responsible for the inefficient surface transport. The M74-F protein will analyzed for functional differences compared to the NiV-F protein. Apart from cell to cell fusion, the M74 surface glycoproteins will also be analyzed for their ability to mediate infection. For this purpose the M74-G and M74-F proteins will be incorporated into pseudovirions based on defective vesicular stomatitis virus. The expected results will not only increase our understanding of the fusion activity of M74, but also provide knowledge what conditions are most promising in attempts to isolate infectious henipaviruses from African bats. This is an important step to analyze these viruses for their potential of interspecies transmission and thus to evaluate their zoonotic risk.