Electrostatic Interactions between Hendra Virus Matrix Proteins Are Required for Efficient Virus-Like-Particle...

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus causing severe disease and high mortality in humans and animals.
• The HeV matrix (M) protein is crucial for viral assembly and budding, but its molecular mechanism remains unclear.
• No structural information was previously available for henipavirus M proteins.

Purpose of the Study:

• To determine the crystal structure of the HeV M protein.
• To elucidate the structural basis of HeV M's role in viral assembly and virus-like particle (VLP) formation.

Main Methods:

• X-ray crystallography to determine the 3D structure of HeV M protein to 2.5-Å resolution.
• Site-directed mutagenesis to disrupt and restore specific protein-protein interactions.
• Virus-like particle (VLP) production assays to assess the functional impact of mutations.

Main Results:

• The crystal structure revealed a dimeric configuration of HeV M, essential for protein stability and VLP formation.
• Key electrostatic interactions between the α1 and α2 helices of neighboring dimers were identified (Arg57, Asp105, Glu108).
• Disruption of these α1-α2 interactions significantly reduced or abolished VLP production, with partial restoration observed in a double mutant.

Conclusions:

• The dimeric structure of HeV M is fundamental for higher-order oligomerization and productive VLP assembly.
• Specific α1-α2 helical interactions involving conserved residues are critical for henipavirus M-driven viral assembly.
• These findings provide the first structural insights into the mechanism of M protein function in henipaviruses.