Fusion glycoprotein F0 (Protein F)

Fusion glycoprotein F0 is a critical transmembrane protein found in many enveloped viruses, responsible for driving the merger of the viral and host cell membranes—an essential step for infection. It is synthesized as an inactive precursor (F0) that requires proteolytic cleavage by host cell enzymes to become functional. This cleavage yields two subunits, F1 and F2, held together by disulfide bonds. The newly exposed hydrophobic fusion peptide at the N-terminus of the F1 subunit is the key effector.

In Nipah virus (NiV), the Fusion protein (F) is a paramount determinant of pathogenicity. Its F0 precursor is cleaved by the host protease furin in the trans-Golgi network, a process that primes the protein for immediate activation upon encountering a target cell. This pre-cleavage is a key reason for NiV's high virulence. The triggering mechanism is tightly coupled to the viral attachment protein G. Specifically, the binding of NiV-G to its cellular receptors (ephrin-B2/B3) transmits a signal that activates the pre-cleaved F protein. This triggers the conformational cascade, deploying the fusion peptide. NiV-F exhibits remarkable pH independence, meaning fusion can occur efficiently at the cell surface without requiring endocytosis. Furthermore, NiV-F and G form a complex that coordinates receptor binding with membrane fusion. Its stability and efficient activation are directly linked to the virus's ability to cause devastating syncytia in infected tissues, contributing to severe encephalitis and systemic pathology.