Sex differences in susceptibility to influenza A virus infection depend on host genotype
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA868295 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21002555.fastq.gz | Fastqsanger.gz | |||
| SRR21002556.fastq.gz | Fastqsanger.gz | |||
| SRR21002557.fastq.gz | Fastqsanger.gz | |||
| SRR21002558.fastq.gz | Fastqsanger.gz | |||
| SRR21002559.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Using influenza A virus (IAV) infection in a mouse model of naturally selected genetic diversity, namely C57BL6/J (B6) mice carrying chromosomes (Chr) derived from the wild-derived and genetically divergent PWD/PhJ (PWD) mouse strain (B6.ChrPWD consomic mice), we examined the effects of genotype and sex on severity of IAV-induced disease To determine the role of genetic variation of host during IAV infection on gene expression, we performed RNAseq analysis on whole lung RNA isolated from two different mice.
2022-08-13 | GSE210905 | GEO
Project description:Infection with the respiratory pathogen influenza A virus (IAV) causes significant morbidity and mortality each year. While host genotype is thought to contribute to severity of disease, naturally occurring genetic determinants remain mostly unknown. Moreover, more severe disease is seen in women compared with men, but genetic mechanisms underlying this sex difference remain obscure. Here, using IAV infection in a mouse model of naturally selected genetic diversity, namely C57BL6/J (B6) mice carrying chromosomes (Chr) derived from the wild-derived and genetically divergent PWD/PhJ (PWD) mouse strain (B6.ChrPWD consomic mice), we examined the effects of genotype and sex on severity of IAV-induced disease. Compared with B6, parental PWD mice were completely protected from IAV-induced disease, a phenotype that was fully recapitulated in the B6.Chr16PWD strain carrying the PWD-derived allele of Mx1. In contrast, several other consomic strains, including B6.Chr3PWD and B6.Chr5PWD, demonstrated greatly increased susceptibility. Notably, B6.Chr5PWD and B6.ChrX.3PWD strains, the latter carrying the distal one-third of ChrX from PWD, exhibited increased morbidity and mortality specifically in male but not female mice. Follow up analyses focused on B6 and B6.ChrX.3PWD strains demonstrated moderately elevated viral load in B6.ChrX3PWD male, but not female mice. Transcriptional profiling demonstrated genotype- and sex-specific gene expression profiles in the infected lung, with male B6.ChrX.3 mice exhibiting the most significant changes, including upregulation of a proinflammatory gene expression program associated with myeloid cells, and altered sex-biased expression of several X-linked genes that represent positional candidates, including Tlr13 and Slc25a53. Taken together, our results identify novel loci on autosomes and the X chromosome regulating IAV susceptibility and demonstrate that sex differences in IAV susceptibility are genotype-dependent, suggesting that future genetic association studies need to consider sex as a covariate.
| S-EPMC9481031 | biostudies-literature
Project description:Seasonal influenza outbreaks and recurrent influenza pandemics present major challenges to public health. By studying immunological responses to influenza in different host species, it may be possible to discover common mechanisms of susceptibility in response to various influenza strains. This could lead to novel therapeutic targets with wide clinical application. Using a mouse-adapted strain of influenza (A/HK/1/68-MA20 [H3N2]), we produced a mouse model of severe influenza (p-flu) that reproduces the hallmark high viral load and overexpression of cytokines associated with susceptibility to p-flu in humans. We mapped genetic determinants of the host response using a panel of 29 closely related mouse strains (AcB/BcA panel of recombinant congenic strains) created from influenza-susceptible A/J and influenza-resistant C57BL/6J (B6) mice. Combined clinical quantitative trait loci (cQTL) and lung expression QTL (eQTL) mapping identified candidate genes for two sex-specific QTLs on chromosomes 2 and 17. The former includes the previously described Hc gene, a deficit of which is associated with the susceptibility phenotype in females. The latter includes the phospholipase gene Pla2g7 and Tnfrsf21, a member of the tumor necrosis factor receptor superfamily. Confirmation of the gene underlying the chromosome 17 QTL may reveal new strategies for influenza treatment. To identify eQTLs, we reanalyzed lung expression data previously obtained by Lee et al (2006) on MGU74Av2 microarrays (Affymetrix) for 54 mice (13BcA, 12AcB, B6 and A/J mice in duplicate) using Custom CDFv12 to reorganize oligonucleotide probes based on the latest genome and transcriptome information. We inferred an A/J or B6 strain of origin for each gene based on the genotype of surrounding markers with a call rate of 96.7%. If a gene was in between A/J and B6 markers for a given RCS, it was coded as NA. Expression values were normalized using the Robust Multi-array Analysis (RMA) for Affymetrix gene chips. To define the association between differentially expressed genes and genotypes, ANOVA was conducted on a per-gene basis using the linear model Expression ~ DSO + BG + DSO*BG, where background (BG) and donor strain of origin (DSO) were coded as binary phenotypes corresponding to A/J or B6. The cutoff for genome-wide significance was computed using the BenjaminiM-bM-^@M-^SHochberg correction. For reference, the paper by Lee (2006): http://www.ncbi.nlm.nih.gov/pubmed/16449383
2012-05-01 | E-GEOD-35888 | biostudies-arrayexpress
Project description:Seasonal influenza outbreaks and recurrent influenza pandemics present major challenges to public health. By studying immunological responses to influenza in different host species, it may be possible to discover common mechanisms of susceptibility in response to various influenza strains. This could lead to novel therapeutic targets with wide clinical application. Using a mouse-adapted strain of influenza (A/HK/1/68-MA20 [H3N2]), we produced a mouse model of severe influenza (p-flu) that reproduces the hallmark high viral load and overexpression of cytokines associated with susceptibility to p-flu in humans. We mapped genetic determinants of the host response using a panel of 29 closely related mouse strains (AcB/BcA panel of recombinant congenic strains) created from influenza-susceptible A/J and influenza-resistant C57BL/6J (B6) mice. Combined clinical quantitative trait loci (cQTL) and lung expression QTL (eQTL) mapping identified candidate genes for two sex-specific QTLs on chromosomes 2 and 17. The former includes the previously described Hc gene, a deficit of which is associated with the susceptibility phenotype in females. The latter includes the phospholipase gene Pla2g7 and Tnfrsf21, a member of the tumor necrosis factor receptor superfamily. Confirmation of the gene underlying the chromosome 17 QTL may reveal new strategies for influenza treatment.
2012-05-02 | GSE35888 | GEO
Project description:Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing conserved influenza epitopes greatly outnumber antibodies reactive against variable epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors.
2022-02-09 | GSE196366 | GEO
Project description:Comparison of gene expression in the lungs of pigs classified as Resistant (RES) or Susceptible (SUS) to influenza pathology based on clinical lesion scores. The aim of the experiment is to identify genes whose expression is associated with resistance/susceptibility to influenza pathology. These are a subset of animals selected from a larger experiment that investigated the effect of low (LBW) or high (HBW) litter birth weight phenotype on influenza pathology.
2015-10-27 | GSE62768 | GEO
Project description:Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection
| PRJNA849180 | ENA
Project description:Coevolutionary change requires reciprocal selection between interacting species, i.e., that the partner genotypes that are favored in one species depend on the genetic composition of the interacting species. Coevolutionary genetic variation is manifested as genotype ´ genotype (G ´ G) interactions for fitness from interspecific interactions. Although quantitative genetic approaches have revealed abundant evidence for G ´ G interactions in symbioses, the molecular basis of this variation remains unclear. Here we study the molecular basis of G ´ G interactions in a model legume-rhizobium mutualism using gene expression microarrays. We find that, like quantitative traits such as fitness, variation in the symbiotic transcriptome may be partitioned into additive and interactive genetic components. Our results suggest that plant genetic variation is the largest influence on nodule gene expression, and that plant genotype and the plant genotype ´ rhizobium genotype interaction determine global shifts in rhizobium gene expression that in turn feedback to influence plant fitness benefits. Moreover, the transcriptomic variation we uncover implicates regulatory changes in both species as drivers of symbiotic gene expression variation. Our study is the first to partition genetic variation in a symbiotic transcriptome, and illuminates potential molecular routes of coevolutionary change. We assayed gene expression using three biological replicates for each plant genotype × rhizobium genotype combination (4 combinations) for a total of 12 chips.
2012-05-01 | GSE29027 | GEO
Project description:Clinical data showed sex variability in the immune response to influenza vaccination, this study aimed to investigate differentially expressed genes that contribute to sex-bias immune responses to quadrivalent inactivated influenza vaccines (QIVs) in older subjects. A cohort of 60 healthy older adults aged 60 to 80 years old were vaccinated with quadrivalent inactivated influenza vaccines (QIVs), and gene expression was analyzed at Day 0 pre-vaccination, Day 3, Day 28 and Day 180 post-vaccination. Sexual dimorphism of humoral immunity was analyzed by HAI assay, and the correlation of gene expression patterns of two sex groups with humoral immune response to vaccination was analyzed. The differentially expressed genes involved in type I interferon signaling pathway and complement activation of classical pathway were upregulated within 3 days post-vaccination in females. At Day 28 after immunization, the immune response showed a man-bias pattern associated with the regulation of protein processing and complement activation of classical pathway. A list of differentially expressed genes associated with variant responses to influenza vaccination between women and men were identified by biology-driven clustering. Old women have a greater immune response to QIVs but rapid decline of antibody levels, while old men have the advantages to sustain a durable response to influenza vaccination. In addition, we identified genes that may contribute to the sex variations toward influenza vaccination in the aged. Our findings highlight the importance of developing personalized seasonal influenza vaccines.
2020-11-09 | GSE151558 | GEO
Project description:Influenza associated bacterial super-infections have devastating impacts on the lung and can result in increased risk of mortality. New strains of influenza circulate throughout the population yearly promoting the establishment of immune memory. Nearly all individuals have some degree of influenza memory prior to adulthood. Due to this we sought to understand the role of immune memory during bacterial super-infections. An influenza heterotypic immunity model was established using influenza A/PR/8/34 and A/X31. We report here that influenza experienced mice are more resistant to secondary bacterial infection with methicillin-resistant Staphylococcus aureus as determined by wasting, bacterial burden, pulmonary inflammation, and lung leak, despite significant ongoing lung remodeling. Multidimensional flow cytometry and lung transcriptomics revealed significant alterations in the lung environment in influenza-experienced mice compared with naïve animals. These include changes in the lung monocyte and T cell compartments, characterized by increased expansion of influenza tetramer specific CD8+ T cells. The protection that was seen in memory experienced mouse model is associated with the reduction in inflammatory mechanisms making the lung less susceptible to damage and subsequent bacterial colonization. These findings provide insight into how influenza heterotypic immunity re-shapes the lung environment and the immune response to a re-challenge event, which is highly relevant to the context of human infection.
2022-06-27 | GSE206095 | GEO