Researchers at Umeå University, Sweden, have shone a light on how poliovirus behaves when it takes over an infected cell and tricks the cell into producing new virus particles. 

It has been known for some time that enteroviruses drastically rearrange the inside of infected cells, and now thanks to the advanced cryo-electron microscope in Umeå, researchers have for the first time been able to take three-dimensional images of how the poliovirus forms and takes over human cells.

“We were surprised to see how the virus transforms processes in the cell that are otherwise used to destroy viruses to produce new viruses instead,” said Lars-Anders Carlson.

The researchers were able to identify the site in the cell where the poliovirus forms new virus particles, by locating sites with half-assembled viruses. This “virus factory” within the cell turned out to be surfaces in the cell that resembled an otherwise normal process in the cell, autophagy.

Autophagy normally serves to break down particles that the cell wants to get rid of, such as virus particles, but the poliovirus is able to reprogramme this defence mechanism  to produce more virus instead.

The VSP34 protein is used by the virus to build new virus particles. When the researchers inhibited VSP34, they could see that the virus could barely assemble whole viruses, but mostly only half virus particles. Another important protein called ULK1 slows down the production of viruses. The researchers could see that the amount of virus exploded when this protein was inhibited, confirming the theory that the poliovirus breaks down this “brake”.

Once the virus has multiplied in the cell, the particles must be released to infect new cells. This is done by releasing the particles in small packets, called vesicles. The researchers found that only viruses that are correctly formed and carry the genetic material of the virus are placed in the vesicles, while empty virus particles are not allowed in.

“The new knowledge we are contributing about the role of autophagy in virus formation may provide new insights for the development of future antivirals that could complement vaccines. We have good reason to believe that our findings are valid for the large group of viruses to which poliovirus belongs, enteroviruses. There is no vaccine against most enteroviruses, but an antiviral that acts on the autophagy system could be effective against many of them. However, there is still a long way to go,’ says Lars-Anders Carlson.

In much of the world, vaccination campaigns have been so successful that the disease was considered virtually eliminated, but in 2022, the virus was again detected in sewage in New York and London. In addition, New York has had the first new case in ten years of a person getting paralysed due to polio infection.

The study was a collaboration with researchers at the National Institutes of Health, USA, and Monash University, Australia. It is published in the scientific journal Nature Communications.

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