The Induction and Consequences of Influenza A Virus-induced Cell Death

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2018 Sep 27

PMID 30254192

Citations 68

Authors

Georgia K Atkin-Smith

Mubing Duan

Weisan Chen

Ivan K H Poon

Affiliations

Soon will be listed here.

Abstract

Infection with Influenza A virus (IAV) causes significant cell death within the upper and lower respiratory tract and lung parenchyma. In severe infections, high levels of cell death can exacerbate inflammation and comprise the integrity of the epithelial cell barrier leading to respiratory failure. IAV infection of airway and alveolar epithelial cells promotes immune cell infiltration into the lung and therefore, immune cell types such as macrophages, monocytes and neutrophils are readily exposed to IAV and infection-induced death. Although the induction of cell death through apoptosis and necrosis following IAV infection is a well-known phenomenon, the molecular determinants responsible for inducing cell death is not fully understood. Here, we review the current understanding of IAV-induced cell death and critically evaluate the consequences of cell death in aiding either the restoration of lung homoeostasis or the progression of IAV-induced lung pathologies.

Citing Articles

Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability.

Mai K, Pan W, Lin Z, Wang Y, Yang Z Adv Biotechnol (Singap). 2025; 3(1):5.

PMID: 39883362 DOI: 10.1007/s44307-025-00057-9.

Effect of pandemic influenza A virus PB1 genes of avian origin on viral RNA polymerase activity and pathogenicity.

Williams S, Qi L, Sheng Z, Xiao Y, Freeman A, Matthews L Sci Adv. 2024; 10(50):eads5735.

PMID: 39671482 PMC: 11641000. DOI: 10.1126/sciadv.ads5735.

Mechanistic Insights into Influenza A Virus-Induced Cell Death and Emerging Treatment Strategies.

Sun Y, Liu K Vet Sci. 2024; 11(11).

PMID: 39591329 PMC: 11598850. DOI: 10.3390/vetsci11110555.

Lauf T, Hader A, Hornung F, Reisser Y, Nietzsche S, Schanz F Immun Ageing. 2024; 21(1):80.

PMID: 39543713 PMC: 11562583. DOI: 10.1186/s12979-024-00482-9.

The Global Trend of Drug Resistant Sites in Influenza A Virus Neuraminidase Protein from 2011 to 2020.

Wang J, Shen B, Yue L, Xu H, Chen L, Qian D Microorganisms. 2024; 12(10).

PMID: 39458365 PMC: 11510644. DOI: 10.3390/microorganisms12102056.

References

Aldridge Jr J, Moseley C, Boltz D, Negovetich N, Reynolds C, Franks J . TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci U S A. 2009; 106(13):5306-11. PMC: 2664048. DOI: 10.1073/pnas.0900655106. View

Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G . Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol. 2010; 11(10):700-14. DOI: 10.1038/nrm2970. View

Kumar P, Thakar M, Ouyang W, Malarkannan S . IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection. Mucosal Immunol. 2012; 6(1):69-82. PMC: 3835350. DOI: 10.1038/mi.2012.49. View

Beyer C, Stearns N, Giessl A, Distler J, Schett G, Pisetsky D . The extracellular release of DNA and HMGB1 from Jurkat T cells during in vitro necrotic cell death. Innate Immun. 2012; 18(5):727-37. PMC: 3724467. DOI: 10.1177/1753425912437981. View

Atkin-Smith G, Poon I . Disassembly of the Dying: Mechanisms and Functions. Trends Cell Biol. 2016; 27(2):151-162. DOI: 10.1016/j.tcb.2016.08.011. View

Wang X, Tan J, Zoueva O, Zhao J, Ye Z, Hewlett I . Novel pandemic influenza A (H1N1) virus infection modulates apoptotic pathways that impact its replication in A549 cells. Microbes Infect. 2013; 16(3):178-86. DOI: 10.1016/j.micinf.2013.11.003. View

McAuley J, Zhang K, McCullers J . The effects of influenza A virus PB1-F2 protein on polymerase activity are strain specific and do not impact pathogenesis. J Virol. 2009; 84(1):558-64. PMC: 2798424. DOI: 10.1128/JVI.01785-09. View

McLean J, Datan E, Matassov D, Zakeri Z . Lack of Bax prevents influenza A virus-induced apoptosis and causes diminished viral replication. J Virol. 2009; 83(16):8233-46. PMC: 2715773. DOI: 10.1128/JVI.02672-08. View

Wang Y, Gao W, Shi X, Ding J, Liu W, He H . Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017; 547(7661):99-103. DOI: 10.1038/nature22393. View

10.

Blachere N, Darnell R, Albert M . Apoptotic cells deliver processed antigen to dendritic cells for cross-presentation. PLoS Biol. 2005; 3(6):e185. PMC: 1084338. DOI: 10.1371/journal.pbio.0030185. View

11.

Shi C, Pamer E . Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011; 11(11):762-74. PMC: 3947780. DOI: 10.1038/nri3070. View

12.

McArthur K, Whitehead L, Heddleston J, Li L, Padman B, Oorschot V . BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science. 2018; 359(6378). DOI: 10.1126/science.aao6047. View

13.

Wei M, Zong W, Cheng E, LINDSTEN T, Panoutsakopoulou V, Ross A . Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001; 292(5517):727-30. PMC: 3049805. DOI: 10.1126/science.1059108. View

14.

Fooladi A, Sattari M, Hassan Z, Mahdavi M, Azizi T, Horii A . In vivo induction of necrosis in mice fibrosarcoma via intravenous injection of type B staphylococcal enterotoxin. Biotechnol Lett. 2008; 30(12):2053-9. DOI: 10.1007/s10529-008-9805-3. View

15.

Wurzer W, Planz O, Ehrhardt C, Giner M, Silberzahn T, Pleschka S . Caspase 3 activation is essential for efficient influenza virus propagation. EMBO J. 2003; 22(11):2717-28. PMC: 158404. DOI: 10.1093/emboj/cdg279. View

16.

Tate M, Deng Y, Jones J, Anderson G, Brooks A, Reading P . Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol. 2009; 183(11):7441-50. DOI: 10.4049/jimmunol.0902497. View

17.

Osterlund P, Pirhonen J, Ikonen N, Ronkko E, Strengell M, Makela S . Pandemic H1N1 2009 influenza A virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons. J Virol. 2009; 84(3):1414-22. PMC: 2812319. DOI: 10.1128/JVI.01619-09. View

18.

Chen W, Calvo P, Malide D, Gibbs J, Schubert U, Bacik I . A novel influenza A virus mitochondrial protein that induces cell death. Nat Med. 2001; 7(12):1306-12. DOI: 10.1038/nm1201-1306. View

19.

Elmore S . Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4):495-516. PMC: 2117903. DOI: 10.1080/01926230701320337. View

20.

Upton J, Sridharan H . InFLUencing host survival: cIAP2 tips the scales. Cell Host Microbe. 2014; 15(1):3-5. DOI: 10.1016/j.chom.2013.12.012. View