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PLoS Biol
. 2023 Jun 13;21(6):e3002097.
doi: 10.1371/journal.pbio.3002097. eCollection 2023 Jun. DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner
Madison S Strine 1 2 , Wesley L Cai 3 , Jin Wei 1 2 4 , Mia Madel Alfajaro 1 2 , Renata B Filler 1 2 , Scott B Biering 5 , Sylvia Sarnik 6 , Ryan D Chow 7 , Ajinkya Patil 8 9 10 , Kasey S Cervantes 8 9 , Clayton K Collings 8 9 , Peter C DeWeirdt 11 , Ruth E Hanna 11 , Kevin Schofield 12 , Christopher Hulme 12 13 , Silvana Konermann 14 15 , John G Doench 11 , Patrick D Hsu 15 16 17 18 , Cigall Kadoch 7 8 19 , Qin Yan 20 21 , Craig B Wilen 1 2 21
Affiliations
Identifying 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.
. 2023 Jun 13;21(6):e3002097.
doi: 10.1371/journal.pbio.3002097. eCollection 2023 Jun. DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner
Madison S Strine 1 2 , Wesley L Cai 3 , Jin Wei 1 2 4 , Mia Madel Alfajaro 1 2 , Renata B Filler 1 2 , Scott B Biering 5 , Sylvia Sarnik 6 , Ryan D Chow 7 , Ajinkya Patil 8 9 10 , Kasey S Cervantes 8 9 , Clayton K Collings 8 9 , Peter C DeWeirdt 11 , Ruth E Hanna 11 , Kevin Schofield 12 , Christopher Hulme 12 13 , Silvana Konermann 14 15 , John G Doench 11 , Patrick D Hsu 15 16 17 18 , Cigall Kadoch 7 8 19 , Qin Yan 20 21 , Craig B Wilen 1 2 21
Affiliations
- PMID: 37310920
- DOI: 10.1371/journal.pbio.3002097
Identifying 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.