Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross
Date
2015Journal
PLoS GeneticsPublisher
Public Library of ScienceType
Article
Metadata
Show full item recordAbstract
New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range of phenotypes relative to classical mouse models of SARS-CoV infection including lung pathology, weight loss and viral titer. Genetic mapping revealed several loci contributing to differential disease responses, including an 8.5Mb locus associated with vascular cuffing on chromosome 3 that contained 23 genes and 13 noncoding RNAs. Integrating phenotypic and genetic data narrowed this region to a single gene, Trim55, an E3 ubiquitin ligase with a role in muscle fiber maintenance. Lung pathology and transcriptomic data from mice genetically deficient in Trim55 were used to validate its role in SARS-CoV-induced vascular cuffing and inflammation. These data establish the Collaborative Cross platform as a powerful genetic resource for uncovering genetic contributions of complex traits in microbial disease severity, inflammation and virus replication in models of outbred populations.Sponsors
Lineberger Comprehensive Cancer Center, University of North Carolina; National Cancer Institute, NCI; National Institute of Allergy and Infectious Diseases, NIAID; National Institutes of Health, NIH: U01CA134240; National Institutes of Health, NIH: U19 AI100625; National Institutes of Health, NIH: U54AI081680Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84946606810&doi=10.1371%2fjournal.pgen.1005504&partnerID=40&md5=a61cbd21f395f0f1cf613b050ecf2336; http://hdl.handle.net/10713/12409ae974a485f413a2113503eed53cd6c53
10.1371/journal.pgen.1005504
Scopus Count
Collections
Related articles
- Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice.
- Authors: Gralinski LE, Menachery VD, Morgan AP, Totura AL, Beall A, Kocher J, Plante J, Harrison-Shostak DC, Schäfer A, Pardo-Manuel de Villena F, Ferris MT, Baric RS
- Issue date: 2017 Jun 7
- Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis.
- Authors: Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, Whitmore A, Heise MT, Baric RS
- Issue date: 2018 Oct 9
- A Multitrait Locus Regulates Sarbecovirus Pathogenesis.
- Authors: Schäfer A, Leist SR, Gralinski LE, Martinez DR, Winkler ES, Okuda K, Hawkins PE, Gully KL, Graham RL, Scobey DT, Bell TA, Hock P, Shaw GD, Loome JF, Madden EA, Anderson E, Baxter VK, Taft-Benz SA, Zweigart MR, May SR, Dong S, Clark M, Miller DR, Lynch RM, Heise MT, Tisch R, Boucher RC, Pardo Manuel de Villena F, Montgomery SA, Diamond MS, Ferris MT, Baric RS
- Issue date: 2022 Aug 30
- Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2'-o-methyltransferase activity.
- Authors: Menachery VD, Yount BL Jr, Josset L, Gralinski LE, Scobey T, Agnihothram S, Katze MG, Baric RS
- Issue date: 2014 Apr
- p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1.
- Authors: Ma-Lauer Y, Carbajo-Lozoya J, Hein MY, Müller MA, Deng W, Lei J, Meyer B, Kusov Y, von Brunn B, Bairad DR, Hünten S, Drosten C, Hermeking H, Leonhardt H, Mann M, Hilgenfeld R, von Brunn A
- Issue date: 2016 Aug 30