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Influence of viral and cellular factors on Nipah virus assembly

The efficient production of infectious viral particles is an important basis for the high pathogenicity and spread of NiV infection in vivo and in vitro. It is known that the formation and release of NiV particles takes place at the plasma membrane of infected cells and is particularly dependent on the viral matrix protein (NiV-M). NiV-M undergoes a complex intracellular transport and then ends up coordinating the assembly of new virions by recruiting NiV surface glycoproteins and viral RNA-containing nucleocapsids to assembly sites (Dietzel et al., 2015). To fulfill this key function, NiV-M proteins, like other viral matrix proteins, form a so-called M-matrix at the plasma membrane. Surprisingly, we observed that NiV nucleocapsids do not align linearly underneath the M matrix, as is known for other paramyxoviruses and as we have shown, for example, for measles viruses (Dietzel et al., 2013). Rather, NiV nucleocapsids accumulate together with NiV-M proteins in large clusters at the plasma membrane of NiV-infected cells (Ringel et al., 2019). Based on the discovery of these unconventional viral structures, we aim to identify the cellular factors and intracellular pathways needed by cytosolic NiV-M proteins to reach the inner plasma membrane and induce cluster formation there. In addition, we want to investigate the functional significance of the plasma membrane clusters, namely, whether they represent a NiV-specific strategy for concentrating components in specialized assembly platforms. This project ultimately aims to uncover the role of plasma membrane clusters in the production of infectious NiV particles and viral spread, and the extent to which NiV-M transport pathways or the cluster structures are suitable targets for a NiV-specific antiviral approach.

NiV-induced plasma membrane-associated clusters, in which NiV-M and viral nucleocapsids accumulate