Virus Assembly Pathways: Straying Away but Not Too Far

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Non-enveloped RNA viruses assemble viral RNA with capsid proteins within host cells.
• In vitro studies show virus-like particles can package non-viral polyanionic molecules, posing a puzzle for in vivo viral RNA selection.
• The precise mechanism of selective viral RNA packaging remains incompletely understood.

Purpose of the Study:

• To investigate the in vitro assembly of brome mosaic virus (BMV) coat proteins with nucleic acid oligomers.
• To elucidate the structures formed during co-assembly and their relationship to native BMV virions.
• To explore potential regulatory pathways for viral RNA packaging in cells.

Main Methods:

• Charge detection mass spectrometry (CDMS) was employed to analyze the mass and stoichiometry of assembled particles.
• Cryo-electron microscopy (cryo-EM) was utilized to determine the high-resolution structures of the assembled complexes.
• In vitro co-assembly experiments were performed using BMV coat proteins and various nucleic acid oligomers.

Main Results:

• Co-assembly of BMV coat proteins and nucleic acid oligomers yielded shell structures distinct from native icosahedral virions.
• These novel structures were found to be strained and less stable compared to the native BMV virion.
• Importantly, these intermediate structures contained significant fragments of native capsid structure, capable of being repurposed.

Conclusions:

• The formation of strained, less stable virus-like particles suggests a potential intermediate stage in viral assembly.
• These structures provide a reservoir of functional capsid components that can be utilized for forming native virions.
• The findings imply a previously unrecognized regulatory mechanism governing selective viral RNA packaging within host cells.