The Spanning Tree Model and the Assembly Kinetics of RNA Viruses

TL;DR

This paper introduces a mathematical model explaining how ssRNA viruses selectively assemble their genomes in host cells, revealing a kinetic proofreading mechanism that enhances specificity during viral assembly.

Contribution

It presents a novel kinetic model demonstrating RNA selection during viral assembly, extending free energy minimization concepts to in vivo conditions.

Findings

Kinetic RNA selection occurs during nucleation complex formation.

Supersaturation and protein-RNA ratio influence selectivity.

Mechanism resembles Hopfield kinetic proofreading.

Abstract

Single-stranded (ss) RNA viruses self-assemble spontaneously in solutions that contain the viral RNA genome molecules and viral capsid proteins. The self-assembly of empty capsids can be understood on the basis of free energy minimization. However, during the self-assembly of complete viral particles in the cytoplasm of an infected cell, the viral genome molecules must be selected from a large pool of very similar host messenger RNA molecules and it is not known whether this also can be understood by free energy minimization. We address this question using a simple mathematical model recently proposed for the assembly of small ssRNA viruses (submitted to PLOS Biocomputation). We present a statistical physics analysis of the properties of the model finding an effect kinetic RNA selection mechanism with selection taking place during the formation of the nucleation complex. Surprisingly, kinetic selectivity is greatly enhanced by a modest level of supersaturation and by reduced protein to RNA concentration ratios. The mechanism is related to the Hopfield kinetic proofreading scenario.