Your browser doesn't support javascript.
loading
Mapping of susceptibility loci for Ebola virus pathogenesis in mice.
Schäfer, Alexandra; Marzi, Andrea; Furuyama, Wakako; Catanzaro, Nicholas J; Nguyen, Cameron; Haddock, Elaine; Feldmann, Friederike; Meade-White, Kimberly; Thomas, Tina; Hubbard, Miranda L; Gully, Kendra L; Leist, Sarah R; Hock, Pablo; Bell, Timothy A; De la Cruz, Gabriela E; Midkiff, Bentley R; Martinez, David R; Shaw, Ginger D; Miller, Darla R; Vernon, Michael J; Graham, Rachel L; Cowley, Dale O; Montgomery, Stephanie A; Schughart, Klaus; de Villena, Fernando Pardo Manuel; Wilkerson, Gregory K; Ferris, Martin T; Feldmann, Heinz; Baric, Ralph S.
Afiliação
  • Schäfer A; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: aschaefe@email.unc.edu.
  • Marzi A; Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA. Electronic address: marzia@niaid.nih.gov.
  • Furuyama W; Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
  • Catanzaro NJ; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Nguyen C; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Haddock E; Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
  • Feldmann F; Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
  • Meade-White K; Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
  • Thomas T; Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
  • Hubbard ML; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Gully KL; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Hock P; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Bell TA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • De la Cruz GE; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Midkiff BR; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Martinez DR; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Shaw GD; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Miller DR; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Vernon MJ; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Graham RL; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Cowley DO; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Animal Models Core Facility, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Montgomery SA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Schughart K; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Institute of Virology, University of Muenster, 48149 Muenster, Germany.
  • de Villena FPM; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Wilkerson GK; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Ferris MT; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Feldmann H; Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: rbaric@email.unc.edu.
Cell Rep ; 43(5): 114127, 2024 May 28.
Article em En | MEDLINE | ID: mdl-38652660
ABSTRACT
Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Predisposição Genética para Doença / Locos de Características Quantitativas / Ebolavirus Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Predisposição Genética para Doença / Locos de Características Quantitativas / Ebolavirus Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article