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

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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.