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DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner.
Strine, Madison S; Cai, Wesley L; Wei, Jin; Alfajaro, Mia Madel; Filler, Renata B; Biering, Scott B; Sarnik, Sylvia; Chow, Ryan D; Patil, Ajinkya; Cervantes, Kasey S; Collings, Clayton K; DeWeirdt, Peter C; Hanna, Ruth E; Schofield, Kevin; Hulme, Christopher; Konermann, Silvana; Doench, John G; Hsu, Patrick D; Kadoch, Cigall; Yan, Qin; Wilen, Craig B.
Afiliação
  • Strine MS; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Cai WL; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Wei J; Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
  • Alfajaro MM; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Filler RB; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Biering SB; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province, China.
  • Sarnik S; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Chow RD; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Patil A; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Cervantes KS; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Collings CK; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • DeWeirdt PC; University of Colorado Boulder, Boulder, Colorado, United States of America.
  • Hanna RE; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Schofield K; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.
  • Hulme C; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
  • Konermann S; Program in Virology, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Doench JG; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.
  • Hsu PD; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
  • Kadoch C; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.
  • Yan Q; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
  • Wilen CB; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
PLoS Biol ; 21(6): e3002097, 2023 06.
Article em En | MEDLINE | ID: mdl-37310920
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Internalização do Vírus / COVID-19 Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Internalização do Vírus / COVID-19 Idioma: En Ano de publicação: 2023 Tipo de documento: Article