MAP3K8 (COT/Tpl-2) is differentially expressed and transcriptionally repressed in models of coronavirus infection.
The coronavirus COVID19 pandemic is an emerging biosafety threat to the nation and the world (1). There are no treatments approved for coronavirus infection in humans (2) and there is a lack of information available regarding the basic transcriptional behavior of human cells and mammalian tissues following coronavirus infection. We mined three independent datasets (3-5), public (3) and published (4, 5) containing transcriptome data from infection models of the Middle East respiratory syndrome (MERS) coronavirus, human coronavirus (HCoV) and SARS coronavirus to discover genes that are differentially expressed in coronaviruses and identify potential therapeutic targets and host cell vulnerabilities. We identified MAP3K8, also known as COT and Tpl-2 (6-8) as a conserved differentially expressed gene following coronavirus infection in primary human cells, in a human cell line, and in the lungs of infected ferrets. MAP3K8 expression dramatically decreased within 12-24 hours of coronavirus infection, both in the lungs of ferrets infected with SARS coronavirus and in primary human microvascular endothelial cells infected with MERS coronavirus. MAP3K8 may be involved in the cellular response to COVID19 infection or a host cell vulnerability, exploited by coronaviruses.