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Researchers have for the first time identified how viruses like the poliovirus and the common cold virus’package up’ their genetic code, allowing them to infect cells.
The findings, published today (Friday, 8 January) in the journal PLOS Pathogens by a team from the Universities of Leeds and York, open up the possibility that medication or anti-viral agents can be developed that would stop such infections.
Once a cell is infected, a virus needs to spread its genetic material to other cells. This is a complex process involving the production of what are known as virions – newly-formed infectious copies of this virus. Each virion is a protein shell containing a complete copy of the virus’s genetic code. The virions can then infect other cells and lead to disease.
What has been a mystery until now is a comprehensive understanding of the way the virus assembles these daughter virions.
Professor Peter Stockley, former Manager of the Astbury Centre for Structural Molecular Biology at Leeds, who part supervised the study with Professor Reidun Twarock from York, said:”This study is extremely important because of the way it shifts our thinking about how we can control some viral diseases. If we can disrupt the mechanism of virion formation, then there’s the capability to stop an infection in its tracks.”
“Our analysis suggests that the molecular characteristics that control the process of virion formation are genetically conserved, meaning they don’t mutate readily – reducing the risk that the virus could change and make any new medication ineffective.”
The study at Leeds and York brings together experts in the molecular structure of viruses, electron microscopy and mathematical biology.
The analysis focuses on a harmless bovine virus that is non-infectious in people, Enterovirus-E, that’s the universally embraced surrogate for the poliovirus. The poliovirus is a dangerous virus that infects people, causing polio and is the goal of a virus eradication initiative by the World Health Organization.
The enterovirus group also includes the human rhinovirus, which causes the common cold.
The study published today details the role of what are called RNA packaging signals, short regions of the RNA molecule which together with proteins in the virus’s casing ensure accurate and efficient formation of an infectious virion.
Using a combination of molecular and mathematical biology, the researchers could determine potential sites on the RNA molecule which could act as packaging signals. Using advanced electron microscopes at the Astbury Biostructure Laboratory in the University of Leeds, scientists were able to directly visualise this process – the first time that’s been possible with any virus of the type.
Understanding in detail how this process works, and the fact that it appears conserved in an entire family of viral pathogens, will enable the pharmaceutical industry to develop anti-viral agents that can block these key interactions and prevent disease.”
Reidun Twarock, Professor
University of Leeds
Chandler-Bostock, R., et al. (2020) Assembly of infectious enteroviruses depends on multiple, conserved genomic RNA-coat protein contacts. PLOS Pathogens. doi.org/10.1371/journal.ppat.1009146.
