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Influenza H3N2 infection of the collaborative cross founder strains reveals highly divergent host responses and identifies a unique phenotype in CAST/EiJ mice
- Source :
- BMC Genomics, BMC Genomics, 17:143. BioMed Central Ltd., BMC genomics, 17(1), 143. England (2016).
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Background 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. Results 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 death/survival counts. Viral load was significantly different between susceptible and resistant strains but not between intermediate and highly susceptible strains. CAST/EiJ mice showed a unique phenotype. Despite high viral loads in their lungs, CAST/EiJ mice exhibited low counts of infiltrating granulocytes and showed increased numbers of macrophages in the lung. Histological studies of infected lungs and transcriptome analyses of peripheral blood cells and lungs confirmed an abnormal response in the leukocyte recruitment in CAST/EiJ mice. Conclusions The eight CC founder strains exhibited a large diversity in their response to influenza infections. Therefore, the CC will represent an ideal mouse genetic reference population to study the influence of genetic variation on the susceptibility and resistance to influenza infections which will be important to understand individual variations of disease severity in humans. The unique phenotype combination in the CAST/EiJ strain resembles human leukocyte adhesion deficiency and may thus represent a new mouse model to understand this and related abnormal immune responses to infections in humans. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2483-y) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
0301 basic medicine
Mice, 129 Strain
Multidisciplinaire, généralités & autres [D99] [Sciences de la santé humaine]
Virulence
Mice, Inbred Strains
Biology
medicine.disease_cause
Mouse model
Mice
03 medical and health sciences
Immune system
Orthomyxoviridae Infections
Genetic variation
Genetics
medicine
Influenza A virus
Animals
Influenza susceptibility
Immune response
Lung
Multidisciplinary, general & others [D99] [Human health sciences]
Disease Resistance
Leukocyte adhesion deficiency
Influenza A Virus, H3N2 Subtype
Strain (biology)
Body Weight
Collaborative cross
Viral Load
medicine.disease
Phenotype
Virology
3. Good health
Mice, Inbred C57BL
030104 developmental biology
Phenotyping
Female
Transcriptome
Viral load
Research Article
Biotechnology
Subjects
Details
- ISSN :
- 14712164
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- BMC Genomics
- Accession number :
- edsair.doi.dedup.....c42223017fda1f3ed6216a47962b8f27