---
title: "Respiratory viruses trigger ferroptosis-like lipid peroxidation and mitochondrial remodeling in lu"
id: "pubmed-42663456"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42663456"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42663456/"
doi: "10.1128/spectrum.01957-26"
published_at: "2026-08-28T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Respiratory viruses trigger ferroptosis-like lipid peroxidation and mitochondrial remodeling in lu
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42663456
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42663456/)
- **DOI:** [10.1128/spectrum.01957-26](https://doi.org/10.1128%2Fspectrum.01957-26)
- **Published At:** 2026-08-28T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Respiratory viruses influenza A virus (IAV) H1N1 and human adenovirus type C5 (HAdV-C5) were compared for induction of **ferroptosis-like** features in lung epithelial cells. - The study used alveolar (A549) and bronchial (BEAS-2B) epithelial cell lines, and primary human epithelial cells were also assessed for mitochondrial effects. - Both IAV H1N1 and HAdV-C5 produced a time-dependent increase in **lipid peroxidation**, a hallmark of ferroptosis. - Lipid peroxidation during infection was partially reduced by the ferroptosis inhibitor **ferrostatin-1**, indicating involvement of ferroptotic processes. - Changes in ferritin protein levels, a key component of **iron homeostasis**, were observed only during late stages of HAdV-C5 infection; details on timing and magnitude were not reported in the abstract. - Both viruses triggered pronounced **mitochondrial network remodeling** in A549, BEAS-2B, and primary epithelial cells, similar to that induced by the ferroptosis inducer **RSL3**; effects varied by cell type and infection stage. - The data suggest that **HAdV-C5**, like **H1N1**, can activate ferroptosis-like processes characterized by lipid peroxidation and mitochondrial dysfunction. - Authors propose these findings deepen understanding of virus-induced lung epithelial cell death and could inform strategies to preserve epithelial barrier integrity during respiratory infections. - Specific experimental protocols, quantitative results, and detailed timelines beyond the abstract summary were not reported in the source abstract.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # Respiratory viruses induce ferroptosis-like features in lung epithelial cells [Ana L Manzano-Covarrubias](https://pubmed.ncbi.nlm.nih.gov/?term=Manzano-Covarrubias+AL&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-2 "Groningen Research Institute for Asthma and COPD \(GRIAC\), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands."), [Alessandra Tosato](https://pubmed.ncbi.nlm.nih.gov/?term=Tosato+A&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Christina H T J Mol-van der Veen](https://pubmed.ncbi.nlm.nih.gov/?term=Mol-van+der+Veen+CH&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Philip Ahmadyar](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmadyar+P&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Jai Walia](https://pubmed.ncbi.nlm.nih.gov/?term=Walia+J&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Manon E Woest](https://pubmed.ncbi.nlm.nih.gov/?term=Woest+ME&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Jacqueline De Vries-Idema](https://pubmed.ncbi.nlm.nih.gov/?term=De+Vries-Idema+J&cauthor_id=42663456)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-3 "Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands."), [Anke Huckriede](https://pubmed.ncbi.nlm.nih.gov/?term=Huckriede+A&cauthor_id=42663456)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-3 "Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands."), [Amalia M Dolga](https://pubmed.ncbi.nlm.nih.gov/?term=Dolga+AM&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Martina Schmidt](https://pubmed.ncbi.nlm.nih.gov/?term=Schmidt+M&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-2 "Groningen Research Institute for Asthma and COPD \(GRIAC\), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands."), [Karim Rafie](https://pubmed.ncbi.nlm.nih.gov/?term=Rafie+K&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#full-view-affiliation-2 "Groningen Research Institute for Asthma and COPD \(GRIAC\), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.") Affiliations Expand ### Affiliations * 1 Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands. * 2 Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. * 3 Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. * PMID: **42663456** * DOI: [ 10.1128/spectrum.01957-26 ](https://doi.org/10.1128/spectrum.01957-26) Item in Clipboard # Respiratory viruses induce ferroptosis-like features in lung epithelial cells Ana L Manzano-Covarrubias et al. Microbiol Spectr. 2026. Show details Display options Display options Format Abstract PubMed PMID Microbiol Spectr Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Microbiol+Spectr%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Microbiol+Spectr%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42663456/) . 2026 Aug 28:e0195726. doi: 10.1128/spectrum.01957-26. Online ahead of print. ### Authors [Ana L Manzano-Covarrubias](https://pubmed.ncbi.nlm.nih.gov/?term=Manzano-Covarrubias+AL&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-2 "Groningen Research Institute for Asthma and COPD \(GRIAC\), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands."), [Alessandra Tosato](https://pubmed.ncbi.nlm.nih.gov/?term=Tosato+A&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Christina H T J Mol-van der Veen](https://pubmed.ncbi.nlm.nih.gov/?term=Mol-van+der+Veen+CH&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Philip Ahmadyar](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmadyar+P&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Jai Walia](https://pubmed.ncbi.nlm.nih.gov/?term=Walia+J&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Manon E Woest](https://pubmed.ncbi.nlm.nih.gov/?term=Woest+ME&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Jacqueline De Vries-Idema](https://pubmed.ncbi.nlm.nih.gov/?term=De+Vries-Idema+J&cauthor_id=42663456)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-3 "Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands."), [Anke Huckriede](https://pubmed.ncbi.nlm.nih.gov/?term=Huckriede+A&cauthor_id=42663456)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-3 "Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands."), [Amalia M Dolga](https://pubmed.ncbi.nlm.nih.gov/?term=Dolga+AM&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands."), [Martina Schmidt](https://pubmed.ncbi.nlm.nih.gov/?term=Schmidt+M&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-2 "Groningen Research Institute for Asthma and COPD \(GRIAC\), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands."), [Karim Rafie](https://pubmed.ncbi.nlm.nih.gov/?term=Rafie+K&cauthor_id=42663456)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-1 "Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42663456/#short-view-affiliation-2 "Groningen Research Institute for Asthma and COPD \(GRIAC\), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.") ### Affiliations * 1 Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands. * 2 Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. * 3 Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. * PMID: **42663456** * DOI: [ 10.1128/spectrum.01957-26 ](https://doi.org/10.1128/spectrum.01957-26) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract During infection, viruses can modulate various regulated cell death (RCD) mechanisms to evade host immunity and enhance replication. However, less is known about how viruses alter the recently discovered RCD ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxidation and mitochondrial fragmentation. Influenza A virus (IAV) H1N1 and human adenovirus type C5 (HAdV-C5) are two common causes of respiratory infections of the upper and lower respiratory tracts and can lead to severe illness. While IAV has been shown to induce ferroptosis to support its replication, less is known about whether this is also true for HAdV-C5. Here, we perform a comparative study investigating ferroptosis features during IAV H1N1 and HAdV-C5 infections using alveolar (A549) and bronchial (BEAS-2B) epithelial cells. Our data reveal that HAdV-C5, similar to H1N1, induces lipid peroxidation in a time-dependent manner, which is partially suppressed in the presence of the ferroptosis inhibitor ferrostatin-1. Strikingly, HAdV-C5 infections only lead to changes in ferritin protein levels, which is responsible for iron storage, during late stages of infection. Furthermore, both H1N1 and HAdV-C5 infections trigger a profound mitochondrial network remodeling in A549, BEAS-2B, and primary human epithelial cells, comparable to that induced by the ferroptosis inducer RSL3, with effects varying by cell type and infection stage. These findings suggest that HAdV-C5, just like H1N1, can activate ferroptosis-like processes, highlighting a potential role for lipid peroxidation and mitochondrial alterations in adenoviral infection. **Importance:** The findings presented here contribute to a deeper understanding of the molecular mechanisms involved in viral infections of the lung epithelium, particularly in the context of virus-induced lung epithelial cell death, a topic of significant relevance to the area of early viral response mechanisms. By elucidating the role of ferroptosis-like hallmarks encompassing lipid peroxidation and mitochondrial dysfunction, our work may inform the development of new therapeutic strategies aimed at enhancing lung epithelial integrity and barrier function, representing the first layer of defense against human pathogens. The topic is of particular importance given the increasing prevalence of antimicrobial resistance. We believe that our research offers significant insights into the field of viral infections and lung disease and would be of great interest to readers in the field of viral biology and respiratory infections. **Keywords:** ferroptosis; human adenovirus C5; influenza A virus; iron homeostasis; lipid peroxidation; mitochondria. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Swine influenza virus triggers ferroptosis in A549 cells to enhance virus replication. ](https://pubmed.ncbi.nlm.nih.gov/35715835/) Cheng J, Tao J, Li B, Shi Y, Liu H.Cheng J, et al.Virol J. 2022 Jun 17;19(1):104. doi: 10.1186/s12985-022-01825-y.Virol J. 2022.PMID: 35715835Free PMC article. * [ Indoleamine 2,3-dioxygenase 1 drives epithelial cells ferroptosis in influenza-induced acute lung injury. ](https://pubmed.ncbi.nlm.nih.gov/40023977/) Zheng Y, Zhang Y, Chen Y, Deng X, Liu B, Xu Q, Qian C, Zhang Z, Wang K, Zeng Y, Liang Z, Sang L, Nong L, Liu X, Xu Y, Li Y, Huang Y.Zheng Y, et al.Redox Biol. 2025 Apr;81:103572. doi: 10.1016/j.redox.2025.103572. Epub 2025 Feb 26.Redox Biol. 2025.
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