The nanoscale organization of the Nipah virus fusion protein informs new membrane fusion mechanisms

Pillar 4
Functional Genomics & Structure-Function of VOCs

Nipah virus (NiV) is a serious respiratory virus that spreads from animals to humans, and symptoms can range from asymptomatic to acute respiratory infection (mild, severe) to fatal encephalitis. This study investigates how NiV merges its membrane with a host cell to initiate infection. Two key proteins drive this process: the attachment protein (NiV-G), which binds to specific host cell surface protein receptors, and the fusion protein (NiV-F), which facilitates the merging of membranes.

NiV-F functions in a similar manner to the human immunodeficiency virus (HIV) envelope, influenza virus hemagglutinin, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike proteins.  The researchers focused on understanding the behavior of NiV-F on the surface of cells and virus-like particles. Using advanced microscopy, they discovered that NiV-F forms dense clusters on these membranes, a pattern that remains consistent regardless of how much protein is present or whether it has undergone a specific cleavage process in the cell to activate it. These clusters seem to help the virus trigger membrane fusion more efficiently.

Further experiments showed that specific regions of the NiV-F protein, including areas where it interacts with itself and parts that embed in the membrane, play a role in forming these clusters. Additionally, interactions with other cell machinery, such as clathrin (a protein involved in shaping cell membranes), help maintain this clustered organization.

The study suggests that the clustering of NiV-F proteins creates a favorable environment for cell membrane fusion by combining molecules in different states of readiness, improving their ability to interact with NiV-G and the host cell surface receptor protein. These findings provide new insights into how the virus’s fusion mechanism works to fuse cell membranes, which could guide future efforts to develop treatments or preventions for Nipah virus and similar viral infections with comparable mechanisms of cell membrane fusion, like measles, parainfluenza virus and other respiratory viruses that result in membrane fusion like SARS-CoV-2.

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