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

蝙蝠被认为是不同病毒家族的主要宿主，包括副粘病毒。高致病性副粘病毒是亨德拉病毒、尼帕病毒（NiV）和亨德拉病毒。它们的天然宿主是在东南亚流行的狐蝠科蝙蝠。基因组亨尼帕病毒RNA最近在非洲蝙蝠的物种Eidolon helvum中被检测到。虽然迄今为止尚未从非洲蝙蝠中分离出传染性亨尼帕病毒，但已显示与非洲蝙蝠接触的人对来自亚洲亨尼帕病毒的抗原呈血清阳性。为了评估病毒从蝙蝠传播到人类的人畜共患风险，有必要分离感染性病毒并分析其复制。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，这些糖蛋白介导病毒与细胞膜之间的融合事件附着到细胞表面并进入细胞，该项目的目的是表征非洲亨尼帕病毒M74的表面蛋白G和F在病毒融合活性中的相互作用。在初步的工作中，已经表明蛋白质在诱导合胞体（即多核巨细胞）的形成方面效率较低。病毒融合活性的这种损害主要是由于M74-G蛋白的低效表面表达。我们希望阐明M74-G的结构元件，这些结构元件是造成表面运输效率低下的原因。将分析M74-F蛋白与NiV-F蛋白相比的功能差异。除了细胞与细胞的融合，还将分析M74表面糖蛋白介导感染的能力。为此目的，将M74-G和M74-F蛋白掺入基于缺陷性水泡性口炎病毒的假病毒体中。预期的结果不仅将增加我们对M74融合活性的理解，而且还将提供知识，在尝试从非洲蝙蝠中分离传染性亨尼帕病毒时，什么条件最有希望。这是分析这些病毒种间传播潜力并由此评估其人畜共患风险的重要步骤。

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.