IMMU-MS07

Mathematical and computational virology

Tuesday, June 15 at 09:30am (PDT)
Tuesday, June 15 at 05:30pm (BST)
Wednesday, June 16 01:30am (KST)

SMB2021 Follow Tuesday (Wednesday) during the "MS07" time block.

Roya Zandi (University of CA, Riverside, USA), Amber Smith (University of Tennessee, USA), Reidun Twarock (University of York, UK)

Description:

This section will address the modelling of viruses at different scales. At the single particle level, we will focus on geometric models of the protein shell called the capsid, which provides protection and transport for the viral genomes, as well as its assembly. This section will also include the repurposing of viral capsids in nanotechnology and therapy. Multi-scale models of replication dynamics within an infected cell, will cover the processes that allow viruses to take over the cellular machinery of infected cells in order to synthesize the building blocks for their progeny, and track the evolution of the viral quasispecies. Due to the wide spectrum of different processes and complexity levels, collaborative efforts of researchers with a range of expertise are required. This section brings together mathematicians, mathematical physicists, biophysicists and biologists to discuss experimental and theoretical challenges at the forefront of virology research. To foster cross-disciplinary communication and identify complementary areas of expertise, sessions include speakers from different disciplines focusing on similar aspects of virology. Key topics include the understanding of virus architecture and assembly including the use and repurposing of viral capsids in nanotechnology, as well as intra- and intercellular infection models.

Carolyn Teschke

(Department of Molecular and Cell Biology, University of Connecticut, USA)

"Using a scaffold to build a viral capsid"

Many dsDNA viruses, including the herpesviruses and tailed bacteriophages, build a precursor capsid called a procapsid into which the dsDNA is subsequently packaged. These viruses require an internal scaffolding protein to assemble coat proteins into procapsids of the proper size and shape. How a scaffolding protein affects the conformation of a coat protein so that it is competent for assembly is not understood. We have used single molecule fluorescence experiments to demonstrate a surprisingly high affinity interaction between bacteriophage P22’s monomeric scaffolding protein and coat protein. This interaction shifts coat protein into a conformation consistent with the procapsid configuration of the protein. Thus, scaffolding protein directly activates coat protein for assembly.

Siyu Li

(Northwestern University, China)

"The physical mechanism of virus self-assembly"

Understanding the basic mechanism of virus self-assembly is fundamental in deciphering the formation and evolution of viruses and exploring their applications to drug delivery, gene therapy and vaccination. While considerable progress has been achieved in determining the virus structures, kinetic pathways by which hundreds or thousands of proteins assemble to form structures with icosahedral order (IO) is still elusive. To decipher the assembly pathway, we developed a computational model to simulate the virus growth. We proposed two mechanisms of small virus assembly: en-mass and nucleation-growth, and studied the role of elasticity and genome in the disorder-order transition process. Moreover, we study the growth of large viruses and discover the universal role of scaffolding proteins in the formation of viral capsids. Using continuum elasticity theory, we show that a nonspecific template not only selects the radius of the capsid, but also leads to the error-free assembly of protein subunits into capsids with universal IO. The mechanism we study will help us deeply understand the correlation between protein building blocks and virus macrostructures, and guide the experiments to explore the possibility of antiviral drugs that inhibit the virus self-assembly.

Trevor Douglas

(Department of Chemistry, Indiana University, Bloomington IN 47405, USA)

"Directed Assembly of Virus-Based Nanoreactors Across Multiple Lengthscales"

The virus like particles (VLP) derived from the bacteriophage P22 provide an opportunity for constructing catalytically functional nano-materials by directed encapsulation of enzyme cargos into the interior volume of the capsid. Directed enzyme encapsulation is achieved by genetically fusing the enzyme of interest to a truncated version of the scaffolding protein, which directs capsid assembly and is encapsulated within the capsid. This approach affords the packing of the desired enzymes within the roughly 60 nm diameter P22 capsid at very high packing density. The self-assembly of these nanoreactors is dependent on the multivalent nature of the cargo and this can be used to control the density of encapsulated cargo. We have explored the molecular level porosity of capsid and determined the range of substrates that can access the encapsulated enzyme and the dependence of this gating on molecular size and charge. Using these P22 nanoreactors as individual building blocks we can extend their utility towards the fabrication of hierarchically complex systems by further manipulation of their exterior surfaces. Superlattice materials, with long-range order, can be assembled through the directed hierarchical assembly of individual P22 particles, mediated by interparticle electrostatic interactions or through interactions of surface bound decoration proteins. In this way we can create ordered 3D materials that exhibit complex coupled behavior through communication between individual P22 nanoreactors.

Giuliana Indelicato

(Department of Mathematics, The University of York, UK)

"The role of surface stress in non-quasi-equivalent viral capsids"

We focus here on viruses in the PRD1-adenovirus lineage which do not always conform to the Caspar and Klug classification. Instead of being built from one type of capsid protein (CP), they either code for multiple distinct structural proteins that break the local symmetry of the capsomers in specific positions, or exhibit auxiliary proteins that stabilize the capsid shell. We investigate the hypothesis that this occurs as a response to mechanical stress. We construct a coarse-grained model of a viral capsid, derived from the experimentally determined atomistic positions of the CPs. For T = 28 viruses in this lineage, which have capsids formed from two distinct structural proteins, we show that the tangential shear stress in the viral capsid concentrates at the sites of local symmetry breaking. In the T = 21, 25 and 27 capsids, we show that stabilizing proteins decrease the tangential stress. These results suggest that mechanical properties can act as selective pressures on the evolution of capsid components, counterbalancing the coding cost imposed by the need for such additional protein components.

Hosted by SMB2021 Follow

Virtual conference of the Society for Mathematical Biology, 2021.