Pillar 3

Processing bodies (PBs) are membraneless granules built of RNA and protein that are found in all cells. PBs control cellular gene expression because they sequester or degrade cellular RNA transcripts. RNAs that shuttle to PBs rarely leave or are successfully translated into protein. Not all cellular RNA transcripts are regulated by PBs. PBs only control the expression of RNAs that encode very important molecules such as those that regulate cell growth or immune responses. That means that PBs regulate the production of proteins that are often elevated in response to an infection, such as proinflammatory cytokines. This is an extra layer of protection that controls the production proteins, such as cytokines, because they have the potential to cause harmful inflammation when present in large amounts. When PBs are lost, this extra checkpoint is blocked. This makes PB loss an important yet underappreciated signal with the potential to exacerbate production of proinflammatory cytokines.

Patients with severe COVID display immune ‘misfiring’ and inflammation. The Corcoran lab at the University of Calgary used their expertise in viruses and PBs to discover a new outcome of SARS-CoV-2 infection. In this study, the Corcoran lab showed PBs were lost after infection with SARS-CoV-2 and the variants of concern Alpha, Beta, Gamma, and Delta, as well as after infection with two common cold human coronaviruses, OC43 and 229E. This makes PB loss a common feature of coronavirus infection. The study also identified that the SARS-CoV-2 nucleocapsid protein was sufficient to cause PB disassembly and re-distribute proinflammatory cytokine RNA transcripts from PBs to the cytoplasm, making them readily available for translation into protein. PB loss altered key RNA transcripts encoding inflammatory cytokines elevated in severe COVID.

This study is important because it suggests that SARS-CoV-2-mediated PB disassembly is a feature of infection that contributes to the dysregulation of proinflammatory cytokine production observed during severe COVID. This study also highlights the complexity of SARS-CoV-2 infection by revealing a new strategy among the multitude of approaches used by this virus to elicit inflammation.

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Mariel Kleer, Rory P. Mulloy, Carolyn-Ann Robinson, Danyel Evseev, Maxwell P. Bui-Marinos, Elizabeth L. Castle, Arinjay Banerjee, Samira Mubareka, Karen Mossman, Jennifer A. Corcoran. Human coronaviruses disassemble processing bodies. PLOS Pathogens 2022.08.23.1010724; https://doi.org/10.1371/journal.ppat.1010724