Influenza H3N2 infection of the collaborative cross founder strains reveals highly divergent host responses and identifies a unique phenotype in CAST/EiJ mice

BMC Genomics
Sarah R LeistKlaus Schughart

Abstract

Influenza A virus is a zoonotic pathogen that poses a major threat to human and animal health. The severe course of influenza infection is not only influenced by viral virulence factors but also by individual differences in the host response. To determine the extent to which the genetic background can modulate severity of an infection, we studied the host responses to influenza infections in the eight genetically highly diverse Collaborative Cross (CC) founder mouse strains. We observed highly divergent host responses between the CC founder strains with respect to survival, body weight loss, hematological parameters in the blood, relative lung weight and viral load. Mouse strain was the main factor with highest effect size on body weight loss after infection, demonstrating that this phenotype was highly heritable. Sex represented another significant main effect, although it was less strong. Analysis of survival rates and mean time to death suggested three groups of susceptibility phenotypes: highly susceptible (A/J, CAST/EiJ, WSB/EiJ), intermediate susceptible (C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ) and highly resistant strains (NZO/HlLtJ, PWK/PhJ). These three susceptibility groups were significantly different with respect to deat...Continue Reading

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Citations

Jan 11, 2017·EMBO Molecular Medicine·Tzipora C Falik-ZaccaiOrly Avni
Sep 6, 2020·Disease Models & Mechanisms·Sarah R LeistDavid R Martinez
Feb 16, 2020·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Heike KollmusMartin Hrabě de Angelis
Sep 26, 2020·Frontiers in Microbiology·Haley N CartwrightAnita K McElroy
Jan 4, 2020·The European Respiratory Journal·Mark Metersky, Grant Waterer
Aug 26, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Hanifa Abu Toamih AtamniFuad A Iraqi
Jun 28, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Heike KollmusKlaus Schughart
Sep 9, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Freeman Suber, Lester Kobzik
Jun 3, 2021·Viruses·Cindy M SpruitRobert P de Vries
Jul 30, 2021·Fluids and Barriers of the CNS·Johanna SchaffenrathAnnika Keller

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Methods Mentioned

BETA
flow cytometry
PCA
RNAseq
amino acid exchange
Feature Extraction
light microscopy
FCS

Software Mentioned

affycoretools
FlowJo
GraphPad Prism
Digital Cell Quantification ( DCQ
limma
clusterProfiler
MmAgilentDesign026655
Feature Extraction
Agi4
VetScan

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