Details

Autor(en) / Beteiligte

• 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.

Titel

Mapping of susceptibility loci for Ebola virus pathogenesis in mice

Ist Teil von

• Cell reports (Cambridge), 2024-05, Vol.43 (5), p.114127-114127, Article 114127

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •CC genetic reference population identifies genetic loci regulating EBOV pathogenesis in mice•An F2 population from two CC lines is either highly resistant or vulnerable to EBOV infection•A major locus on chromosome 7, encoding Trim5, drives severe EVD-like disease in mice•Gene expression signatures of liver damage mirror severe EVD in humans Schäfer et al. use a genetic screening platform based on the collaborative cross (CC) to identify and elucidate the role of the Trim5 locus during Ebola virus (EBOV) infection and the development of EBOV disease (EVD) in mice.