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SARS-CoV-2 Orphan Gene ORF10 Contributes to More Severe COVID-19 Disease.
Haltom, Jeffrey; Trovao, Nidia S; Guarnieri, Joseph; Vincent, Pan; Singh, Urminder; Tsoy, Sergey; O'Leary, Collin A; Bram, Yaron; Widjaja, Gabrielle A; Cen, Zimu; Meller, Robert; Baylin, Stephen B; Moss, Walter N; Nikolau, Basil J; Enguita, Francisco J; Wallace, Douglas C; Beheshti, Afshin; Schwartz, Robert; Wurtele, Eve Syrkin.
Afiliación
  • Haltom J; Department of Genetics Development and Cell Biology, Iowa State University, Ames, IA 50011, USA.
  • Trovao NS; Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Guarnieri J; COVID-19 International Research Team, Medford, MA 02155, USA.
  • Vincent P; Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, 20892, USA.
  • Singh U; COVID-19 International Research Team, Medford, MA 02155, USA.
  • Tsoy S; Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • O'Leary CA; COVID-19 International Research Team, Medford, MA 02155, USA.
  • Bram Y; Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, 20892, USA.
  • Widjaja GA; Bioinformatics and Computational Biology Program, and Genetics Program, Iowa State University, Ames, IA 50011, USA.
  • Cen Z; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • Meller R; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
  • Baylin SB; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • Moss WN; Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Nikolau BJ; Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Enguita FJ; Morehouse School of Medicine, Atlanta, GA , 30310-1495, USA.
  • Wallace DC; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231.
  • Beheshti A; Van Andel Research Institute, Grand Rapids, MI 49503.
  • Schwartz R; Bioinformatics and Computational Biology Program, and Genetics Program, Iowa State University, Ames, IA 50011, USA.
  • Wurtele ES; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
medRxiv ; 2023 Nov 27.
Article en En | MEDLINE | ID: mdl-38076862
The orphan gene of SARS-CoV-2, ORF10, is the least studied gene in the virus responsible for the COVID-19 pandemic. Recent experimentation indicated ORF10 expression moderates innate immunity in vitro. However, whether ORF10 affects COVID-19 in humans remained unknown. We determine that the ORF10 sequence is identical to the Wuhan-Hu-1 ancestral haplotype in 95% of genomes across five variants of concern (VOC). Four ORF10 variants are associated with less virulent clinical outcomes in the human host: three of these affect ORF10 protein structure, one affects ORF10 RNA structural dynamics. RNA-Seq data from 2070 samples from diverse human cells and tissues reveals ORF10 accumulation is conditionally discordant from that of other SARS-CoV-2 transcripts. Expression of ORF10 in A549 and HEK293 cells perturbs immune-related gene expression networks, alters expression of the majority of mitochondrially-encoded genes of oxidative respiration, and leads to large shifts in levels of 14 newly-identified transcripts. We conclude ORF10 contributes to more severe COVID-19 clinical outcomes in the human host.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: MedRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: MedRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos