Sex disparities in influenza: A multiscale network analysis

Chang Wang, Lauren P. Lashua, Chalise E. Carter, Scott K. Johnson, Minghui Wang, Ted M. Ross, Elodie Ghedin, Bin Zhang, Christian V. Forst

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish
Article number104192
Issue number5
StatePublished - 20 May 2022


  • Biological sciences
  • Immunology
  • Systems biology
  • Virology


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