Journal Article Preprint Epublish 1 citation
PubMed: 40766393 DOI: 10.1101/2025.07.29.667514
Gasdermin E is Dispensable for H1N1 Influenza Virus Pathogenesis in Mice.
bioRxiv
Authors: Samuel Speaks, Jonathan Papa, Matthew McFadden, Jack E Roettger, Benjamin D Liu, Shreenath Mohan, Brendan M Reznik, Steve Leumi, Jana M Cable, Adriana Forero, Jacob S Yount
Affiliations
- Department of Microbial Infection and Immunity, Wexner College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
- Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA.
- Department of Microbial Infection and Immunity, Wexner College of Medicine, The Ohio State University, Columbus, OH 43210, USA. Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA.
Abstract
Targeting cell death pathways, including pyroptosis and necroptosis, has been shown to mitigate influenza virus infection severity. Here, we examined whether pyroptosis specifically driven by the pore-forming protein gasdermin E (GSDME) is involved in regulating influenza virus infection outcomes. We found that mice showed similar weight loss and survival in severe A/PR/8/34 (H1N1) virus infections compared to WT counterparts. Likewise, lung dysfunction, histopathological damage, viral titers, and inflammatory cytokine levels were similar in the two groups. Global transcriptomic analysis also revealed similar inflammatory and antiviral gene expression programs in WT versus mouse lungs at baseline and in response to infection. To confirm the generality of these findings, we infected mice with 2009 pandemic H1N1 virus and again observed similar weight loss, mortality, and lung dysfunction in WT and mice. Our results overall demonstrate that GSDME contributes negligibly to the host response against H1N1 influenza virus, refining our understanding of cell death pathways in influenza pathogenesis.
MeSH
Cells, Genes, Lung, Influenza, Human, Viruses, Pyroptosis, Weight Loss, Cell Death, Orthomyxoviridae, Infections, Virus Diseases