Structural plasticity of mumps virus nucleocapsids with cryo-EM structures

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Mumps virus (MuV) is a contagious pathogen causing global outbreaks.
• MuV, like other mononegaviruses, has a single-stranded negative-sense RNA genome.
• The viral nucleocapsid, formed by nucleoproteins, is crucial for genome management and viral replication.

Purpose of the Study:

• To elucidate the molecular mechanisms behind Mumps virus nucleocapsid structural plasticity.
• To understand how Mumps virus nucleocapsid conformational changes facilitate different viral activities.
• To provide high-resolution structural insights into Mumps virus nucleocapsid assembly and genome condensation.

Main Methods:

• Cryo-electron microscopy was employed to determine near-atomic resolution structures.
• In vitro assembly of Mumps virus nucleoprotein-RNA complexes was analyzed.
• Structural analysis focused on nucleocapsid states, including rings, filaments, and helical structures.

Main Results:

• Two Mumps virus nucleoprotein-RNA rings (13 and 14 protomers), a stacked-ring filament, and two distinct helical nucleocapsids were resolved.
• Structures revealed dense and hyperdense states of the Mumps virus nucleocapsid.
• The C-terminal tail of the nucleoprotein appears to regulate helical nucleocapsid assembly and transitions between states.

Conclusions:

• The study provides a molecular mechanism for the structural plasticity observed in Mumps virus nucleocapsids.
• Findings suggest a link between nucleocapsid structural plasticity and efficient genome condensation.
• These insights are critical for understanding Mumps virus replication and for developing antiviral strategies.