Virus Assembly Pathways inside a Host Cell

TL;DR

This study uses simulations to explore how viral RNA and coat proteins assemble into shells within host cells, revealing mechanisms behind the formation of non-icosahedral intermediates that can reassemble into stable virus structures.

Contribution

The paper uncovers how coat proteins assemble around nucleic acids forming metastable non-icosahedral cages, providing insight into virus assembly pathways amid cellular complexity.

Findings

Coat proteins can form non-icosahedral cages around RNA.

These cages are strained and can split into fragments.

Metastable intermediates can reassemble into stable shells.

Abstract

Simple RNA viruses self-assemble spontaneously and encapsulate their genome into a shell called the capsid. This process is mainly driven by the attractive electrostatic interaction between the positive charges on capsid proteins and the negative charges on the genome. Despite its importance and many decades of intense research, how the virus selects and packages its native RNA inside the crowded environment of a host cell cytoplasm in the presence of an abundance of non-viral RNA and other anionic polymers, has remained a mystery. In this paper, we perform a series of simulations to monitor the growth of viral shells and find the mechanism by which cargo-coat protein interactions can impact the structure and stability of the viral shells. We show that coat protein subunits can assemble around a globular nucleic acid core by forming non-icosahedral cages, which have been recently observed in assembly experiments involving small pieces of RNA. We find that the resulting cages are strained and can easily be split into fragments along stress lines. This suggests that such metastable non-icosahedral intermediates could be easily re-assembled into the stable native icosahedral shells if the larger wild-type genome becomes available, despite the presence of myriad of non-viral RNAs.