RNA sequencing of SARS-CoV and SARS-CoV-2 N proteins expressing cell lines

SARS-CoV and SARS-CoV-2, the causative agents of severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), are genetically related positive-sense RNA viruses that may cause similar pathophysiology. Despite host could activate interferon responses upon coronaviral infection to suppress virus replication, both SARS-CoV and SARS-CoV-2 have evolved strategies to inhibit interferon response. Here, we constructed SARS-CoV and SARS-CoV-2 N proteins expressing cell lines (HEK293T-N and HEK293T-2N) and performed RNA sequencing analysis, showing that both SARS-CoV-2 and SARS-CoV N proteins could inhibit expression of early growth response gene 1 (EGR1) to suppress interferon response. Moreover, EGR1 could degrade N proteins of SARS-CoV and SARS-CoV-2 in a lysosome-dependent manner, and inhibit viral replication of SARS-CoV-2. Our findings revealed the important role of EGR1 in host innate immune response against SARS-CoV and SARS-CoV-2, which would contribute to understanding the pathogenesis of human coronaviruses and development of antiviral therapies. In addition, we demonstrated that both N proteins could upregulate expression of nervous development-related genes, which may be associated with the neurological symptoms of COVID-19 and SARS patients. We constructed the Flag-tagged SARS-CoV and SARS-CoV-2 N proteins (N and 2N) stably-expressing HEK293T cell lines, Flag-tagged GFP stably-expressing HEK293T cell line was used as a control. The cell lines were transfected with or without poly (I:C). At 24 hours post transfection, cells were collected for RNA sequencing at Majorbio (http://www.majorbio.com/).