Simple Models and Simple Analyses of Virus Capsid Assembly

A Zlotnick

doi:10.1080/10273660500149943

Abstract

Assembly of even a simple virus is a complex reaction. Yet, in many cases, the capsids of isometric viruses assemble spontaneously and with high fidelityin vitro.In vitroreactions can be used as the basis for interpreting assemblyin vivo, searching for assembly-directed small molecules, or subverting normal assembly to generate novel structures. A model is required to interpret experimental observation of any complex reaction. To this end, we developed a thermodynamickinetic (master equation) model, in which assembly is described in terms of a cascade of low order reactions. The resulting model can readily be adjusted to match the specific features of a biological system. Simulations replicate experimental observations of assembly and lead to experimentally testable predictions. Analyses based on a basic model, in which only a single path from monomer to capsid was posited, are equally applicable to sparse and complete models that include selected intermediates and every possible intermediate, respectively.

Highlights

Viruses are parsimonious with their resources and profligate with those of their host
Structures with icosahedral symmetry make the most efficient use of the genome and the host [1] as they can be divided into 60 identical asymmetric units, while the symmetry groups of all other Platonic solids permit only a smaller number of asymmetric units
Pseudo-T 1⁄4 3 poliovirus assembles from 12 to 15 mers, each comprised of five heterotrimers [3]; papovaviruses assemble from 72 pentamers [4]; many T 1⁄4 3 plant viruses, such as cowpea chlorotic mottle virus (CCMV), assemble from 90 dimers [5]; T 1⁄4 4 hepatitis B virus (HBV) assembles from dimers [6]

Summary

ZLOTNICK*

Of even a simple virus is a complex reaction. In many cases, the capsids of isometric viruses assemble spontaneously and with high fidelity in vitro. In vitro reactions can be used as the basis for interpreting assembly in vivo, searching for assembly-directed small molecules, or subverting normal assembly to generate novel structures. A model is required to interpret experimental observation of any complex reaction. To this end, we developed a thermodynamic–kinetic (master equation) model, in which assembly is described in terms of a cascade of low order reactions. Analyses based on a basic model, in which only a single path from monomer to capsid was posited, are applicable to sparse and complete models that include selected intermediates and every possible intermediate, respectively

Introduction

Model calculations

Model predictions recapitulate experimental observation

Conclusions and future directions