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Pirbright scientists uncover new clues in coronavirus replication

Pirbright Institute NS21048- Coronavirus.jpg
Study shows, for the first time, that replication of RNA in host cells happens in a separate compartment within the cell.

More clues about coronavirus replication in humans and animals have been uncovered by researchers at Pirbright. This research fills in important knowledge gaps that could help to control disease caused by a range of coronaviruses in the future.

When we think of coronaviruses, we think of SARS-CoV-2, however there are several other coronaviruses that cause disease in both humans and animals. Human coronaviruses include a strain known as HCoV 229E which can cause the common cold. Coronaviruses that can cause severe human diseases include severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the most recent and well-known coronavirus, SARS-CoV-2.

Coronaviruses are also prevalent in animal health, causing welfare concerns and economic issues. Porcine epidemic diarrhea virus affects pigs, bovine coronavirus can be found in cattle and avian infectious bronchitis virus is common in poultry. It is therefore important to improve the understanding of how these viruses interact with their host, and with that knowledge find ways to control the spread of disease.

In this recent study published in Viruses, Pirbright scientists showed, for the first time, that replication of coronavirus genetic material (RNA) in host cells happens in a separate compartment within the cell. These compartments are likely to provide a way to protect the RNA from being recognized by the cell's natural defenses which could spark an immune response and prevent the virus replicating.

Viruses are 'obligate intracellular parasites' which means they need the host cell to do the work to replicate all parts of the virus, package them up and release them to infect other cells. Viruses do this in 'virus factories.' These are areas in the cell where viruses are efficiently replicated, while also hiding from the cell's defense mechanisms against viral infection.

In addition to this being investigated for avian infectious bronchitis virus, researchers also explored how RNA is replicated by other viruses in the coronavirus family (there are four different types). Interestingly, they discovered that RNA replication is similar across all coronaviruses, including SARS-CoV-2.

"Knowing that all coronaviruses replicate viral RNA within a membrane-bound compartment is a significant step in understanding the replication of this important virus family," says Dr. Helena Maier, head of the Coronavirus Cellular Biology group at Pirbright. "This discovery could prove important when thinking about how to control the spread of diseases caused by coronaviruses, and how to protect human and animal health. This research could one day lay the foundations for new antiviral discoveries to target viral replication and control disease, which would not only be important for livestock, such as poultry that are affected by infectious bronchitis, but also humans who have been significantly impacted by outbreaks of SARS, MERS and SARS-CoV-2."

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