Human coronaviruses disassemble processing bodies

Abstract

AbstractThe Coronaviridae are a family of viruses with large RNA genomes. Seven coronaviruses (CoVs) have been shown to infect humans, including the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19). The host response to CoV infection is complex and regulated, in part, by intracellular antiviral signaling pathways triggered in infected cells. Pathogenic CoVs can hijack these antiviral responses, reshaping the production of interferons and proinflammatory cytokines. Processing bodies (PBs) are membraneless ribonucleoprotein granules that mediate decay or translational suppression of cellular mRNAs; this is particularly relevant for proinflammatory cytokine mRNA which normally reside in PBs and are repressed. PBs or their components are believed to play important direct-acting antiviral roles, providing a compelling reason for their frequent disassembly by many viruses. Prior to this report, no information was known about how human CoVs impact PBs. Here, we show that three human CoVs, SARS-CoV-2 and the common cold CoVs, OC43 and 229E, induce PB loss. Moreover, we screened a SARS-CoV-2 gene library and identified that expression of the viral nucleocapsid (N) protein from SARS- CoV-2 was sufficient to mediate PB disassembly. N protein mediated PB loss correlated with elevated transcript levels of selected proinflammatory cytokines that would normally be repressed in PBs. Ectopic expression of the N proteins from four other human coronaviruses (OC43, MERS, 229E and NL63) did not cause PB disassembly, suggesting that this feature is unique to SARS-CoV-2 N protein. These data indicate that SARS-CoV-2 disassembles PBs during infection. As an unintended side effect, the disassembly of PBs may enhance levels of proinflammatory cytokine mRNAs which normally reside in PBs, thereby reshaping the subsequent immune response.