Respiratory Syncytial Virus Matrix Protein Induces Lung Epithelial Cell Cycle Arrest Through a P53 Dependent Pathway

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jun 5

PMID 22662266

Citations 29

Authors

Tao Bian

John D Gibbs

Claes Orvell

Farhad Imani

Affiliations

Soon will be listed here.

Abstract

Respiratory syncytial virus (RSV) is the major cause of viral respiratory infections in children. Our previous study showed that the RSV infection induced lung epithelial cell cycle arrest, which enhanced virus replication. To address the mechanism of RSV-induced cell cycle arrest, we examined the contribution of RSV-matrix (RSV-M) protein. In this report, we show that in both the A549 cell line and primary human bronchial epithelial (PHBE) cells, transfection with RSV-M protein caused the cells to proliferate at a slower rate than in control cells. The cell cycle analysis showed that RSV-M protein induced G1 phase arrest in A549 cells, and G1 and G2/M phase arrest in PHBE cells. Interestingly, RSV-M expression induced p53 and p21 accumulation and decreased phosphorylation of retinoblastoma protein (Rb). Further, induction of cell cycle arrest by RSV-M was not observed in a p53-deficient epithelial cell line (H1299). However, cell cycle arrest was restored after transfection of p53 cDNA into H1299 cells. Taken together, these results indicate that RSV-M protein regulates lung epithelial cell cycle through a p53-dependent pathway, which enhances RSV replication.

Citing Articles

RNA-RNA interactions between respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity.

Ressel S, Kumar S, Bermudez-Barrientos J, Gordon K, Lane J, Wu J Nucleic Acids Res. 2024; 52(9):4872-4888.

PMID: 38412296 PMC: 11109944. DOI: 10.1093/nar/gkae116.

APOBEC3G Is a p53-Dependent Restriction Factor in Respiratory Syncytial Virus Infection of Human Cells Included in the p53/Immune Axis.

Gladwell W, Yost O, Li H, Bell W, Chen S, Ward J Int J Mol Sci. 2023; 24(23).

PMID: 38069117 PMC: 10706465. DOI: 10.3390/ijms242316793.

Reshaping Our Knowledge: Advancements in Understanding the Immune Response to Human Respiratory Syncytial Virus.

Attaianese F, Guiducci S, Trapani S, Barbati F, Lodi L, Indolfi G Pathogens. 2023; 12(9).

PMID: 37764926 PMC: 10536346. DOI: 10.3390/pathogens12091118.

Respiratory Syncytial Virus: A Comprehensive Review of Transmission, Pathophysiology, and Manifestation.

Kaler J, Hussain A, Patel K, Hernandez T, Ray S Cureus. 2023; 15(3):e36342.

PMID: 37082497 PMC: 10111061. DOI: 10.7759/cureus.36342.

Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?.

Amiama-Roig A, Perez-Martinez L, Rodriguez Ledo P, Verdugo-Sivianes E, Blanco J Microorganisms. 2023; 11(3).

PMID: 36985286 PMC: 10051562. DOI: 10.3390/microorganisms11030713.

References

Ghildyal R, Mills J, Murray M, Vardaxis N, Meanger J . Respiratory syncytial virus matrix protein associates with nucleocapsids in infected cells. J Gen Virol. 2002; 83(Pt 4):753-757. DOI: 10.1099/0022-1317-83-4-753. View

Restle A, Janz C, Wiesmuller L . Differences in the association of p53 phosphorylated on serine 15 and key enzymes of homologous recombination. Oncogene. 2005; 24(27):4380-7. DOI: 10.1038/sj.onc.1208639. View

Shay D, Holman R, Newman R, Liu L, Stout J, Anderson L . Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA. 1999; 282(15):1440-6. DOI: 10.1001/jama.282.15.1440. View

Yi F, Saha A, Murakami M, Kumar P, Knight J, Cai Q . Epstein-Barr virus nuclear antigen 3C targets p53 and modulates its transcriptional and apoptotic activities. Virology. 2009; 388(2):236-47. PMC: 4287381. DOI: 10.1016/j.virol.2009.03.027. View

Casavant N, Luo M, Rosenke K, Winegardner T, Zurawska A, Fortunato E . Potential role for p53 in the permissive life cycle of human cytomegalovirus. J Virol. 2006; 80(17):8390-401. PMC: 1563868. DOI: 10.1128/JVI.00505-06. View

Cowton V, McGivern D, Fearns R . Unravelling the complexities of respiratory syncytial virus RNA synthesis. J Gen Virol. 2006; 87(Pt 7):1805-1821. DOI: 10.1099/vir.0.81786-0. View

Oster B, Bundgaard B, Hollsberg P . Human herpesvirus 6B induces cell cycle arrest concomitant with p53 phosphorylation and accumulation in T cells. J Virol. 2005; 79(3):1961-5. PMC: 544083. DOI: 10.1128/JVI.79.3.1961-1965.2005. View

Yao X, Mouland A, Subbramanian R, Forget J, Rougeau N, Bergeron D . Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells. J Virol. 1998; 72(6):4686-93. PMC: 109992. DOI: 10.1128/JVI.72.6.4686-4693.1998. View

Kash J, Walters K, Davis A, Sandouk A, Schwartzman L, Jagger B . Lethal synergism of 2009 pandemic H1N1 influenza virus and Streptococcus pneumoniae coinfection is associated with loss of murine lung repair responses. mBio. 2011; 2(5). PMC: 3175626. DOI: 10.1128/mBio.00172-11. View

10.

Orba Y, Suzuki T, Makino Y, Kubota K, Tanaka S, Kimura T . Large T antigen promotes JC virus replication in G2-arrested cells by inducing ATM- and ATR-mediated G2 checkpoint signaling. J Biol Chem. 2009; 285(2):1544-54. PMC: 2801279. DOI: 10.1074/jbc.M109.064311. View

11.

Oster B, Kofod-Olsen E, Bundgaard B, Hollsberg P . Restriction of human herpesvirus 6B replication by p53. J Gen Virol. 2008; 89(Pt 5):1106-1113. DOI: 10.1099/vir.0.83262-0. View

12.

Royds J, Hibma M, Dix B, Hananeia L, Russell I, Wiles A . p53 promotes adenoviral replication and increases late viral gene expression. Oncogene. 2005; 25(10):1509-20. DOI: 10.1038/sj.onc.1209185. View

13.

Levine A, Oren M . The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 2009; 9(10):749-58. PMC: 2771725. DOI: 10.1038/nrc2723. View

14.

Liu H, Lin P, Lee J, Hsu H, Shih W . Retardation of cell growth by avian reovirus p17 through the activation of p53 pathway. Biochem Biophys Res Commun. 2005; 336(2):709-15. PMC: 7092890. DOI: 10.1016/j.bbrc.2005.08.149. View

15.

Graham B, Perkins M, Wright P, Karzon D . Primary respiratory syncytial virus infection in mice. J Med Virol. 1988; 26(2):153-62. DOI: 10.1002/jmv.1890260207. View

16.

Chulu J, Huang W, Wang L, Shih W, Liu H . Avian reovirus nonstructural protein p17-induced G(2)/M cell cycle arrest and host cellular protein translation shutoff involve activation of p53-dependent pathways. J Virol. 2010; 84(15):7683-94. PMC: 2897625. DOI: 10.1128/JVI.02604-09. View

17.

Sato Y, Shirata N, Murata T, Nakasu S, Kudoh A, Iwahori S . Transient increases in p53-responsible gene expression at early stages of Epstein-Barr virus productive replication. Cell Cycle. 2010; 9(4):807-14. DOI: 10.4161/cc.9.4.10675. View

18.

Ghildyal R, Ho A, Jans D . Central role of the respiratory syncytial virus matrix protein in infection. FEMS Microbiol Rev. 2006; 30(5):692-705. DOI: 10.1111/j.1574-6976.2006.00025.x. 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.

Emmett S, Dove B, Mahoney L, Wurm T, Hiscox J . The cell cycle and virus infection. Methods Mol Biol. 2004; 296:197-218. PMC: 7120536. DOI: 10.1385/1-59259-857-9:197. View