What makes viruses so infectious?

Researchers from the Universities of Leeds and York have identified for the first time the way viruses like the poliovirus and the common cold virus ‘package up’ their genetic code, allowing them to infect cells. Their findings, published in the journal PLOS Pathogens, open up the possibility that drugs or antiviral 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 creation of what are known as virions — newly formed infectious copies of the virus. Each virion is a protein shell containing a complete copy of the virus’s genetic code, so the virions can then go on and infect other cells, causing disease. But what has been a mystery until now is a detailed understanding of the way the virus assembles these daughter virions.

“Our analysis suggests that the molecular features that control the process of virion formation are genetically conserved, meaning they do not mutate easily — reducing the risk that the virus could change and make any new drugs ineffective,” said Professor Peter Stockley from the University of Leeds, who part supervised the research with York’s Professor Reidun Twarock.

“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 is the potential to stop an infection in its tracks.”

The researchers’ study focused on a harmless bovine virus that is non-infectious in people, enterovirus-E, which is the universally adopted surrogate for the poliovirus — a dangerous virus that is the target of a virus eradication initiative by the World Health Organization (WHO). The study detailed the role of RNA packaging signals — short regions of the RNA molecule which, together with proteins from the virus’s casing, ensure accurate and efficient formation of an infectious virion.

Using a combination of molecular and mathematical biology, the researchers were able to identify possible sites on the RNA molecule that could act as packaging signals. Using advanced electron microscopes at the Astbury Biostructure Laboratory at the University of Leeds, the scientists were able to directly visualise this process — the first time that has been possible with any virus of this 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 antiviral agents that can block these key interactions and prevent disease,” Professor Twarock said.

Image caption: A visualisation of an enterovirus-E virion assembling. Capsid protein pentamers are recruited to the growing protein shell (brown) during virion assembly by formation of sequence-specific contacts between the genome (packaging signals shown as orange space-filled models) and the enterovirus-E capsid.

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