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Genetic loci regulate Sarbecovirus pathogenesis: A comparison across mice and humans.
Schäfer, Alexandra; Gralinski, Lisa E; Leist, Sarah R; Hampton, Brea K; Mooney, Michael A; Jensen, Kara L; Graham, Rachel L; Agnihothram, Sudhakar; Jeng, Sophia; Chamberlin, Steven; Bell, Timothy A; Scobey, D Trevor; Linnertz, Colton L; VanBlargan, Laura A; Thackray, Larissa B; Hock, Pablo; Miller, Darla R; Shaw, Ginger D; Diamond, Michael S; de Villena, Fernando Pardo Manuel; McWeeney, Shannon K; Heise, Mark T; Menachery, Vineet D; Ferris, Martin T; Baric, Ralph S.
Afiliación
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: aschaefe@email.unc.edu.
  • Gralinski LE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: lgralins@email.unc.edu.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Hampton BK; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Mooney MA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Division of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, OR, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Po
  • Jensen KL; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Graham RL; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Agnihothram S; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Jeng S; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA.
  • Chamberlin S; Division of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, OR, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA.
  • Bell TA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Scobey DT; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Linnertz CL; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • VanBlargan LA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Thackray LB; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Hock P; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Miller DR; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Shaw GD; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology2, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology3, Washington University School of Medicine, St. Louis, MO, USA.
  • de Villena FPM; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • McWeeney SK; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Division of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, OR, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Po
  • Heise MT; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina, Chapel Hill NC,
  • Menachery VD; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston TX, USA; Department of Pathology and Center for Biodefense & Emerging Infectious Diseases, University of Te
  • Ferris MT; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: mtferris@email.unc.edu.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina, Chapel Hill
Virus Res ; 344: 199357, 2024 06.
Article en En | MEDLINE | ID: mdl-38508400
ABSTRACT
Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we deleted a candidate interferon stimulated gene, Trim14 which resulted in enhanced SARS-CoV titers and clinical disease, suggesting an antiviral role during infection. Importantly, about 60 % of the murine QTL encode susceptibility genes identified as priority candidates from human genome-wide association studies (GWAS) studies after SARS-CoV-2 infection, suggesting that similar selective forces have targeted analogous genes and pathways to regulate Sarbecovirus disease across diverse mammalian hosts. These studies provide an experimental platform in rodents to investigate the molecular-genetic mechanisms by which potential cross mammalian susceptibility loci and genes regulate type-specific and cross-SARS-like group 2B CoV replication, immunity, and pathogenesis in rodent models. Our study also provides a paradigm for identifying susceptibility loci for other highly heterogeneous and virulent viruses that sporadically emerge from zoonotic reservoirs to plague human and animal populations.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sitios de Carácter Cuantitativo Límite: Animals / Humans Idioma: En Revista: Virus Res Asunto de la revista: VIROLOGIA Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sitios de Carácter Cuantitativo Límite: Animals / Humans Idioma: En Revista: Virus Res Asunto de la revista: VIROLOGIA Año: 2024 Tipo del documento: Article