Physics of Viruses: The Role of Genome and Membrane
We study the physics of virus assembly. The dissertation can be separated into two parts. The first part focuses on spherical single stranded (ss) RNA viruses or virus like particles. Using mean-field theory, we explore the role of the secondary structure of RNA on the viral assembly by modeling the RNA as an annealed branched polymer. Our results verify that RNA branchedness maximizes the amount of encapsulated genome into a relatively small capsid and makes assembly more efficient. We furthermore offer an explanation for the phenomena of overcharging observed in viral particles. Chapter 5 demonstrates an application of our theory to satellite tobacco mosaic virus (STMV). Our theory explains, energetically, why a truncated RNA is encapsidated by STMV capsid proteins more favorably.
In the second part, we explore the role of genome on the structure of human immunodeficiency virus (HIV) shells (Chapter 6). Our analytical results show that the free energy of confinement of genome into a conical capsid is less than that for a cylindrical one when the genome does not interact with the capsid as in in vivo experiments. This may explain why the conical structures favor over the cylindrical ones in in vivo. In Chapter 7, we carry out coarse-grained simulations to examine the HIV maturation pathways and the role of genome and membrane on the formation of conical shells. We show that the membrane restricts the growth of the otherwise extended incomplete shell and induces local stresses causing formation of the pentamers necessary for the assembly of closed conical or tubular shells. More interestingly, we find that any asymmetry developed in the growing lattice due to interaction with the membrane or genome, or due to the shape of initial immature lattice creates conical capsids, as opposed to cylindrical shells. Furthermore, our work confirms that viruses employ all the accessible pathways to maturation, explaining many aspects of the previous HIV pathway experiments.