ArticleCirculation research2021
Influenza Causes MLKL-Driven Cardiac Proteome Remodeling During Convalescence.
Article in Circulation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Research progress on the association between viruses and cardiac diseases.Journal of virology · 2026Review
- Influenza hijacks myeloid cells to inflict type-I interferon-fueled damage in the heart.Immunity · 2026Article
- ZBP1-driven cell death in severe influenza.Trends in microbiology · 2025Review
- Cardiomyocyte-specific NHE1 overexpression confers protection against myocardial infarction during hyperglycemia.Cardiovascular diabetology · 2025Article
- Establishment and Evaluation of Fatigue Mice Model in the Convalescence Phase of Influenza A.Viruses · 2025Article
- Mechanistic Insights into Influenza A Virus-Induced Cell Death and Emerging Treatment Strategies.Veterinary sciences · 2024Review
- Targeting necroptosis: a promising avenue for respiratory disease treatment.Cell communication and signaling : CCS · 2024Review
- Need for standardization of Influenza A virus-induced cell death in vivo to improve consistency of inter-laboratory research findings.Cell death discovery · 2024Review
- COVID-19 HEART unveiling as atrial fibrillation: pathophysiology, management and future directions for research.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2023Review
- Major adverse cardiovascular events are associated with necroptosis during severe COVID-19.Critical care (London, England) · 2023Observational
- Necroptosis Drives Major Adverse Cardiovascular Events During Severe COVID-19.Research square · 2023Article
- Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis.Biomolecules · 2023Review
- Nonrespiratory sites of influenza-associated disease: mechanisms and experimental systems for continued study.The FEBS journal · 2022Review
- Article
- Kinetic Multi-omic Analysis of Responses to SARS-CoV-2 Infection in a Model of Severe COVID-19.Journal of virology · 2021Article
- The Role of the Key Effector of Necroptotic Cell Death, MLKL, in Mouse Models of Disease.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
rationalePatients with and without cardiovascular diseases have been shown to be at risk of influenza-mediated cardiac complications. Recent clinical reports support the notion of a direct link between laboratory-confirmed influenza virus infections and adverse cardiac events.
objectiveDefine the molecular mechanisms underlying influenza virus-induced cardiac pathogenesis after resolution of pulmonary infection and the role of necroptosis in this process. METHODS AND
resultsHearts from wild-type and necroptosis-deficient (MLKL [mixed lineage kinase domain-like protein]-KO) mice were dissected 12 days after initial influenza A virus (IAV) infection when viral titers were undetectable in the lungs. Immunofluorescence microscopy and plaque assays showed presence of viable IAV particles in the myocardium without generation of interferon responses. Global proteome and phosphoproteome analyses using high-resolution accurate mass-based LC-MS/MS and label-free quantitation showed that the global proteome as well as the phosphoproteome profiles were significantly altered in IAV-infected mouse hearts in a strain-independent manner. Necroptosis-deficient mice had increased survival and reduced weight loss post-IAV infection, as well as increased antioxidant and mitochondrial function, indicating partial protection to IAV infection. These findings were confirmed in vitro by pretreatment of human and rat myocytes with antioxidants or necroptosis inhibitors, which blunted oxidative stress and mitochondrial damage after IAV infection.
conclusionsThis study provides the first evidence that the cardiac proteome and phosphoproteome are significantly altered post-pulmonary influenza infection. Moreover, viral particles can persist in the heart after lung clearance, altering mitochondrial function and promoting cell death without active replication and interferon responses. Finally, our findings show inhibition of necroptosis or prevention of mitochondrial damage as possible therapeutic interventions to reduce cardiac damage during influenza infections. Graphic Abstract: A graphic abstract is available for this article.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.