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

• Applicant: Professor Dr. Georg Herrler
• Subject Area: Virology
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256633021

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.

• DFG Programme: Research Grants