Cryo-electron tomography of Nipah virus structural protein complexes in virus-like particles

Area of Science:

• Virology
• Structural Biology
• Cell Biology

Background:

• Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus.
• The matrix protein (M) is crucial for NiV assembly, mediating interactions between viral components and the host cell membrane.
• Full-length protein interactions within NiV membrane complexes remain poorly understood.

Purpose of the Study:

• To elucidate the structural organization and protein:protein interactions of key Nipah virus structural proteins (M, N, F, G).
• To investigate the role of these interactions in virion assembly and morphology.

Main Methods:

• Cryo-electron tomography (cryo-ET) was employed to visualize virus-like particles (VLPs).
• Subtomogram averaging was used to determine high-resolution structures of protein complexes within VLPs.
• Structural analysis focused on the matrix protein (M) lattice and its interactions with glycoproteins (F/G) and ribonucleoprotein complexes (N).

Main Results:

• A novel M-dimer arrangement was resolved at 7Å resolution, featuring two distinct repeating holes.
• Filamentous hemagglutinin (F) trimers were observed to associate with one specific hole, influenced by F's cytoplasmic tail.
• G glycoproteins localized to areas of higher VLP curvature, while N protein significantly increased VLP pleomorphism.

Conclusions:

• The study reveals unprecedented details of Nipah virus matrix protein organization and its interactions with other structural proteins.
• These findings provide critical insights into the mechanisms governing paramyxoviral assembly, structure, and the morphological diversity of virions.
• The identified M-dimer structure and protein associations offer potential targets for antiviral strategies.