@article{1475492b57fb40cdac65c4c540388d5e,
title = "Sex disparities in influenza: A multiscale network analysis",
abstract = "Sex differences in the pathogenesis of infectious diseases because of differential immune responses between females and males have been well-documented for multiple pathogens. However, the molecular mechanism underlying the observed sex differences in influenza virus infection remains poorly understood. In this study, we used a network-based approach to characterize the blood transcriptome collected over the course of infection with influenza A virus from female and male ferrets to dissect sex-biased gene expression. We identified significant differences in the temporal dynamics and regulation of immune responses between females and males. Our results elucidate sex-differentiated pathways involved in the unfolded protein response (UPR), lipid metabolism, and inflammatory responses, including a female-biased IRE1/XBP1 activation and male-biased crosstalk between metabolic reprogramming and IL-1 and AP-1 pathways. Overall, our study provides molecular insights into sex differences in transcriptional regulation of immune responses and contributes to a better understanding of sex biases in influenza pathogenesis.",
keywords = "Biological sciences, Immunology, Systems biology, Virology",
author = "Chang Wang and Lashua, {Lauren P.} and Carter, {Chalise E.} and Johnson, {Scott K.} and Minghui Wang and Ross, {Ted M.} and Elodie Ghedin and Bin Zhang and Forst, {Christian V.}",
note = "Funding Information: This work was funded by grants and contracts from the National Institutes of Health ( R21 AI149013 , U01 AI111598 , RF1AG054014 , U01 AG046170 , and 75N93019C00052 ). This work was funded in part by the Division of Intramural Research (DIR) at NIAID / NIH (EG). In addition, T.M.R. is supported by the Georgia Research Alliance as an Eminent Scholar. Funding Information: This work was funded by grants and contracts from the National Institutes of Health (R21 AI149013, U01 AI111598, RF1AG054014, U01 AG046170, and 75N93019C00052). This work was funded in part by the Division of Intramural Research (DIR) at NIAID/NIH (EG). In addition, T.M.R. is supported by the Georgia Research Alliance as an Eminent Scholar. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Ni-ka Ford (Instructional Technology Group at ISMMS) is being acknowledged for designing the artwork of the graphical abstract. C.V.F. conceived the project. C.W. and C.V.F. performed the computational study. M.W. helped with RNAseq data processing. E.G. and T.M.R. designed the experiments. L.P.L. C.E.C. and S.K.J. executed the experiments. B.Z. helped with the computational analysis and provided guidance. C.W. and C.V.F. wrote the manuscript. All the authors reviewed the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = may,
day = "20",
doi = "10.1016/j.isci.2022.104192",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "5",
}