2D phase transitions infect viruses

In collaboration with the Institut de Chimie des Substances Naturelles and the Université François Rabelais, we have found a way to describe the thermal disassembly of viral particles as a first-order phase transition. By mapping the icosahedral capsid structure onto a two-dimensional lattice, we have established an expression of the melting temperature as a function of the interaction parameters between subunits. Fluorescence experiments performed with a plant virus have validated the theoretical description.

Grand canonical Monte Carlo simulations and a mean-field theory have allowed us to obtain an analytical expression for the melting temperature of a viral capsid as a funcion of the short-range attractive energy between subunits, their effective charge and the Debye screening length characteristic of the electrostatic interactions. Fluorescence experiments carried out with a plant virus – the cowpea chlorotic mottle virus (CCMV) – have corroborated the model and enabled the measurement of the interaction parameters between subunits, with both empty and genomic RNA-filled capsids. An accurate knowledge of the disassembly phenomena and of the interaction energies that come into play should prove itself essential in the development of disassembly inhibitors for therapeutic purpose.

Crystal structure of the cowpea chlorotic mottle virus capsid (left) and two-dimensional lattice (right) used to reproduce thermal disassembly in Monte Carlo simulations. [Phys. Rev. Applied 7 (2017) 014005]

Weighing polymers packaged in viral capsids

Viruses are ubiquitous pathogens in all kingdoms of life and are major public health issues as well as serious economic and veterinary concerns worldwide. The simplest viruses consist of an icosahedral protein shell called capsid protecting the genome encoded in one or more polynucleotide chains. Many of these viruses self-assemble in their host cells and capture the required segments of their genome with a remarkable selectivity. Whether such a level of selectivity is due to intricate molecular recognitions or to nonspecific interactions between genome and capsid is much debated question.

We applied the contrast variation method in small-angle neutron scattering on capsids derived from cowpea chlorotic mottle virus (CCMV) and containing a deuterated synthetic negatively charged polymer, the poly(styrene sulfonic acid). The experiments performed with the D22 diffractometer of the Institut Laue Langevin in Grenoble allowed us to measure separately and with an unprecedented accuracy the total mass of packaged polymer as well as that of the capsid, for a wide range of polymer molecular weights. It turned out that the mass ratio – or equivalently, the charge ratio – is invariant with the polymer molecular weight. To do so, capsids either package several chains simultaneously, or selectively retain the shortest chains that could fit the capsid interior. These results demonstrate that the remarkable selectivity of viral proteins for packaging polymers can be essentially explained by thermodynamic principles involving electrostatic interactions. They shed light into the nonspecific origin of the genome selectivity for many viral systems including CCMV.

(a) Crystal structure of CCMV. The icosahedral capsid has a diameter of 28 nm and is made of 180 copies of a single viral protein adopting three different conformations labelled in cyan, red and green. (b) Chemical structure of poly(styrene sulfonic acid) used in its deuterated form throughout this study. (c) Principle of the contrast variation method applied on polymer-filled capsids. In 100% H2O, both capsid (gray) and polymer (cyan) contribute to the scattered intensity. In 43% D2O, capsid is contrast matched and only polymer is visible, whereas in 100% D2O, the intensity is solely due to capsid and polymer is contrast matched. (d) Electron microscopy images of empty (top) and polymer-filled (bottom) CCMV capsids. Notice that the latter are smaller than the former. [Phys. Rev. Lett. 113 (2014) 128305]

Related publications

  • J. CHEN, M. CHEVREUIL, S. COMBET, Y. LANSAC, G. TRESSET (2017) Investigating the thermal dissociation of viral capsid by lattice model. J. Phys. Condens. Matter 29 474001.
  • G. TRESSET, J. CHEN, M. CHEVREUIL, N. NHIRI, E. JACQUET, Y. LANSAC (2017) Two-dimensional phase transition of viral capsid gives insights into subunit interactions. Phys. Rev. Applied 7 014005.
  • G. TRESSET, M. TATOU, C. LE COEUR, M. ZEGHAL, V. BAILLEUX, A. LECCHI, K. BRACH, M. KLEKOTKO, L. PORCAR (2014) Weighing polyelectrolytes packaged in viruslike particles. Phys. Rev. Lett. 113 128305.
  • G. TRESSET, V. DECOUCHE, J.-F. BRYCHE, A. CHARPILIENNE, C. LE COEUR, C. BARBIER, G. SQUIRES, M. ZEGHAL, D. PONCET, S. BRESSANELLI (2013) Unusual self-assembly properties of Norovirus Newbury2 virus-like particles. Arch. Biochem. Biophys. 537 144-152.


Guillaume Tresset