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Pirbright study uncovers replication sites of emerging pig disease

Important insights into the replication mechanisms of porcine deltacoronavirus (PDCoV) could facilitate the development of broad-spectrum control methods to tackle diseases caused by coronaviruses.

11 December 2019
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A recent study carried out at The Pirbright Institute has uncovered the sites within the cell where porcine deltacoronavirus (PDCoV) makes new copies of itself during replication. Using electron microscopy, Pirbright scientists demonstrated that the virus creates replication organelles that are similar to other coronaviruses. Establishing that this step in the virus life cycle is consistent across the virus family could facilitate the development of broad-spectrum control methods to tackle the diseases they cause.

Identified in 2012, PDCoV is an emerging Deltacoronavirus that infects pigs and causes severe diarrhoea and can lead to the death of piglets. Replication sites created by viruses during infection, known as replication organelles, have been well characterised in the other three genera of the coronavirus family (Alpha-, Beta-, and Gammacoronavirus). Pirbright researchers explored the structures formed by PDCoV when replicating, predicting that they would be comparable to the rest of the family.

Published in the journal Viruses, the research confirmed that PDCoV hijacks the host cell’s machinery to form two different structures that make up the replication organelle, shown in the image below. These structures are highly similar to those created by infectious bronchitis virus (IBV), a Gammacoronavirus that causes debilitating disease in chickens.

Electron micrograph of the two replication organelle structures. White arrows indicate double membrane vesicles and the black bracket encompasses the small circular spherules which protrude from the zippered endoplasmic reticulum (ER) that appear as tubular shapes.
Electron micrograph of the two replication organelle structures. White arrows indicate double membrane vesicles and the black bracket encompasses the small circular spherules which protrude from the zippered endoplasmic reticulum (ER) that appear as tubular shapes.

“Imaging porcine deltacoronavirus during host cell infection provides an important insight into the replication mechanisms used by this group of viruses”, said Dr Helena Maier, Head of the Nidovirus-Cell Interactions group at Pirbright. “This is particularly important since other Deltacoronaviruses cannot be adapted to cell culture, which makes it very challenging to study how they replicate and interact with the host cellular machinery.”

As well as providing information about the Deltacoronavirus genera, this study has helped identify common structures formed by coronaviruses when they infect a host cell. “This evidence suggests that there may be specific interactions that are consistent across the family that we could target to engineer vaccines and antivirals, as well as informing animal breeding programmes for coronavirus resistance”, added Dr Maier.

The research will feed into the group’s broader programme of work that aims to understand how the coronavirus family interacts with host cells. Future research will use sophisticated, high-resolution three-dimensional imaging techniques, such as cryo-electron tomography and cryo-soft X-ray tomography, to view the replication organelles of infectious bronchitis virus (IBV), which will allow the team to investigate host-virus interactions in greater detail. The planned research will use Diamond Light Source facilities as part of a new collaboration agreed with Pirbright in November 2019.

December 10, 2019 - Pirbright

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