Peter Stockley (Biochemistry, Astbury Centre for Structural Molecular Biology, University of Leeds, UK)
Abstract:Viral particles (virions) are obligate intermediates in all viral lifecycles, acting both as protective containers between rounds of infection and cell-specific delivery vehicles for the genomic nucleic acid at the start of the next infection cycle. For viruses containing only proteins and nucleic acids, infectious particles can often be produced in vitro by simply mixing the components, implying that self-assembly is an inherent function of the viral components. Such assemblies show sophistication beyond our current ability to manipulate matter synthetically. Particles often contain hundreds of identical polypeptide chains organised into icosahedral lattices. Assembly in vivo is highly efficient, producing thousands of identical progeny particles for every one that initiates an infection. This process includes successful encapsidation of cognate viral nucleic acid in the presence of large amounts of potentially competing cellular equivalents. I will discuss the challenges faced by viral machines in these processes and the molecular mechanisms they have evolved to optimise the efficiency and fidelity of virion assembly and genome packaging. The focus will be on viruses with single-stranded RNA genomes, a major group of pathogens in every kingdom of life, that are responsible for many fatal or debilitating human and animal diseases, as well as devastating losses of major crop plants. I will show that their RNA genomes play essential co-operative roles in virion assembly, that can only be fully understood via a combination of biological, physical and mathematical techniques. I will show that assembly is intimately linked to genome disassembly/uncoating and how these mechanisms allow viruses to avoid the natural self-defense mechanisms of their hosts, such as RNA silencing.