Surface glycoproteins of two bat paramyxoviruses: functional characterization and importance for host switch

近年来，蝙蝠被认为是许多病毒的主要宿主。有时，病毒会成功地跨越物种障碍，引起可能对受影响的人或动物致命的感染。例如引起严重急性呼吸综合征(SARS)或中东呼吸综合征(MERS)的冠状病毒，或副粘病毒科亨尼帕病毒属中的尼帕病毒。在蝙蝠身上检测病毒核酸的尝试已经相当成功，但从蝙蝠中分离传染性病毒仍然是一项具有挑战性的任务。到目前为止，还没有一份关于成功从蝙蝠身上分离到冠状病毒的报告。在这种情况下，限制因素似乎是病毒与细胞表面受体的相互作用。就副粘病毒而言，虽然病毒总数相当低，但成功分离的病毒为数不多。这使得很难评估病毒的人畜共患潜力以及对人和动物的危险。然而，最近有两个有趣的发现，使我们能够更详细地分析蝙蝠病毒的趋向性，从而更好地了解这些感染性病原体。类似尼帕的埃尼帕病毒只在东南亚分离到。然而，在非洲蝙蝠身上也检测到了基因组RNA。我们首次证明了非洲埃尼帕病毒(G和F)的表面糖蛋白具有生物活性。它们诱导合胞体形成的能力，即多核巨细胞，表明这些糖蛋白具有功能性的受体结合和融合活性。在拟议的项目中，我们将更详细地分析G和F的生物活性以及它们介导感染的能力。这些知识将为非洲埃尼帕病毒的成功分离提供基础。对蝙蝠副粘病毒基因组RNA的检测发现，存在一种与腮腺炎病毒密切相关的病毒。利用这种腮腺炎样蝙蝠病毒的表面糖蛋白(HN和F)，我们也能够诱导合胞体的形成。与上述非洲埃尼帕病毒类似，我们将更详细地分析这两种糖蛋白的生物学活性。在这种情况下，我们将为人类腮腺炎病毒的突变分析提供基础，该分析将揭示哪些氨基酸交换对人类病毒向蝙蝠病毒的转变至关重要。

In recent years, bats have been recognized as a major reservoir for a number of viruses. From time to time, viruses succeed in crossing the species barriers and cause infections that may be lethal for the affected humans or animals. Examples are the coronaviruses responsible for the severe acute respiratory syndrome (SARS) or the Middle East respiratory syndrome (MERS), or the Nipah virus within the family Paramyxoviridae, genus Henipavirus.Attempts to detect viral nucleic acid in bats have been quite successful; however, to isolate infectious virus from bats is still a challenging task. So far, there is not a single report about a successful isolation of a coronavirus from bats. In this case, the limiting factor appears to be the interaction of the viruses with receptors on the cell surface. As far as paramyxoviruses are concerned, there were a few successful virus isolations, though the total number is rather low. This makes it difficult to evaluate the zoonotic potential of the viruses and the danger for man and animals. However, there have been two interesting findings recently that allow us to analyze the tropism of bat viruses in more detail and thus to get a better knowledge about these infectious agents. Nipah-like henipaviruses have been isolated only in South East Asia. However, genomic RNA has been detected also in African bats. We have shown for the first time that the surface glycoproteins of an African henipavirus (G and F) have biological activities. Their ability to induce the formation of syncytia, i.e. multinucleated giant cells, shows that these glycoproteins have a functional receptor-binding as well as fusion activity. In the proposed project, we will analyze the biological activities of G and F as well as their ability to mediate infection in more detail. This knowledge will provide a basis for the successful isolation of an African henipavirus.The detection of genomic RNA from paramyxoviruses in bats revealed the presence of a virus that is closely related to mumps virus. With the surface glycoproteins (HN and F) of this mumps-like bat virus we were also able to induce syncytia formation. Similar to the above mentioned African henipavirus, we will analyze the biological activities of the two glycoproteins in more detail. In this case, we will provide the basis for a mutational analysis of the human mumps virus that will reveal which amino acid exchanges are crucial for the transition of the human virus to the bat virus.