DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner

Madison S. Strine, Wesley L. Cai, Jin Wei, Mia Madel Alfajaro, Renata B. Filler, Scott B. Biering, Sylvia Sarnik, Ryan D. Chow, Ajinkya Patil, Kasey S. Cervantes, Clayton K. Collings, Peter C. DeWeirdt, Ruth E. Hanna, Kevin Schofield, Christopher Hulme, Silvana Konermann, John G. Doench, Patrick D. Hsu, Cigall Kadoch, Qin YanCraig B. Wilen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

AU Identifying: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly host genes essential for Severe Acute Respiratory : Syndrome Coronavirus 2 (SARS-CoV-2) has the potential to reveal novel drug targets and further our understanding of Coronavirus Disease 2019 (COVID-19). We previously performed a genome-wide CRISPR/Cas9 screen to identify proviral host factors for highly pathogenic human coronaviruses. Few host factors were required by diverse coronaviruses across multiple cell types, but DYRK1A was one such exception. Although its role in coronavirus infection was previously undescribed, DYRK1A encodes Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A and is known to regulate cell proliferation and neuronal development. Here, we demonstrate that DYRK1A regulates ACE2 and DPP4 transcription independent of its catalytic kinase function to support SARS-CoV, SARS-CoV-2, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) entry. We show that DYRK1A promotes DNA accessibility at the ACE2 promoter and a putative distal enhancer, facilitating transcription and gene expression. Finally, we validate that the proviral activity of DYRK1A is conserved across species using cells of nonhuman primate and human origin. In summary, we report that DYRK1A is a novel regulator of ACE2 and DPP4 expression that may dictate susceptibility to multiple highly pathogenic human coronaviruses.

Original languageEnglish (US)
Article numbere3002097
JournalPLoS biology
Volume21
Issue number6 June
DOIs
StatePublished - Jun 2023

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences

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