Coordinated interactions among Nipah virus N, P and M proteins drive formation of distinct inclusion bodies

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus.
• NiV forms two distinct membrane-less organelles: cytosolic inclusion bodies (IBs) for RNA synthesis and plasma membrane-associated inclusion bodies (IB-PMs) for assembly and budding.

Purpose of the Study:

• To identify essential protein domains and interactions driving the formation of NiV's distinct inclusion bodies.
• To elucidate the molecular mechanisms underlying NiV RNA synthesis and particle formation through IB characterization.

Main Methods:

• Investigated the roles of NiV nucleocapsid (N) and phospho (P) proteins in forming cytosolic IB-like structures.
• Analyzed the necessity of matrix protein, N, and P proteins for IB-PM-like structure formation.
• Assessed the liquid-like properties and internal fluidity of different IB types.

Main Results:

• Specific domains of N and P proteins are essential for liquid-like cytosolic IB formation.
• Dual-site interactions between N and P proteins are required for generating these liquid organelles.
• Matrix protein, N, and P proteins are indispensable for forming IB-PM-like structures with reduced internal fluidity.

Conclusions:

• NiV utilizes specific protein-protein interactions to create spatially and functionally distinct inclusion bodies.
• These findings provide novel insights into the molecular mechanisms of viral RNA synthesis and particle formation in NiV.
• Understanding NiV's organelle formation is key to developing antiviral strategies.