Virus Assembly Pathways Inside a Host Cell.

Area of Science:

• Structural Biology
• Virology
• Computational Biophysics

Background:

• Simple RNA viruses spontaneously self-assemble, encapsulating their genome within a protein shell (capsid).
• This process is primarily driven by electrostatic interactions between positively charged capsid proteins and the negatively charged viral RNA genome.
• The mechanism of selective viral RNA packaging in a crowded cellular environment, amidst abundant non-viral nucleic acids, remains poorly understood.

Purpose of the Study:

• To investigate the mechanism of viral shell assembly and the impact of cargo-coat protein interactions on viral shell structure and stability.
• To elucidate how viruses select and package their native RNA genome within the host cell cytoplasm.

Main Methods:

• A series of computational simulations were performed to monitor viral shell growth.
• The study focused on analyzing the interactions between coat proteins and nucleic acid cargo.
• Simulations examined the formation and stability of viral shell structures.

Main Results:

• Coat protein subunits can assemble around a globular nucleic acid core, forming non-icosahedral cages.
• These non-icosahedral cages, observed in recent experiments with small RNA fragments, are structurally strained.
• The strained cages can fragment along stress lines, indicating they are metastable intermediates.

Conclusions:

• Metastable non-icosahedral intermediates can readily reassemble into stable, native icosahedral shells upon the availability of the larger, wild-type viral genome.
• This suggests a potential mechanism for selective viral RNA packaging, even in the presence of numerous competing non-viral RNAs.
• The findings provide insights into the dynamics of viral assembly and genome selection.