title: Role of dietary antioxidants in human metapneumovirus infection.
abstract: Human metapneumovirus (hMPV) is a major cause of respiratory tract infections in children, elderly and immunocompromised hosts, for which no vaccine or treatment are currently available. Oxidative stress and inflammatory responses represent important pathogenic mechanism(s) of hMPV infection. Here, we explored the potential protective role of dietary antioxidants in hMPV infection. Treatment of airway epithelial cells with resveratrol and quercetin during hMPV infection significantly reduced cellular oxidative damage, inflammatory mediator secretion and viral replication, without affecting viral gene transcription and protein synthesis, indicating that inhibition of viral replication occurred at the level of viral assembly and/or release. Modulation of proinflammatory mediator expression occurred through the inhibition of transcription factor nuclear factor (NF)-κB and interferon regulatory factor (IRF)-3 binding to their cognate site of endogenous gene promoters. Our results indicate the use of dietary antioxidants as an effective treatment approach for modulating hMPV induced lung oxidative damage and inflammation.
authors: Departments of Pediatrics, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. Electronic address: nakomara@utmb.edu.
authors: Narayana
authors: N
authors: Komaravelli
authors: Departments of Pediatrics, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors: John P
authors: JP
authors: Kelley
authors: Departments of Pediatrics, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors: Matteo P
authors: MP
authors: Garofalo
authors: Departments of Pediatrics, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors: Haotian
authors: H
authors: Wu
authors: Departments of Pediatrics, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors: Antonella
authors: A
authors: Casola
authors: Departments of Pediatrics, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors: Deepthi
authors: D
authors: Kolli
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D019587:Dietary Supplements / Q000032:analysis*; D006801:Humans; D029121:Metapneumovirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D018184:Paramyxoviridae Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D011794:Quercetin / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016207:Cytokines; D013267:Stilbenes; D011794:Quercetin; D000077185:Resveratrol
keywords: Human metapneumovirus; Quercetin; Resveratrol
references: Free Radic Biol Med. 2004 May 15;36(10):1199-207
references: 15110384
references: Cell Host Microbe. 2008 Mar 13;3(3):158-67
references: 18329615
references: Virology. 2007 Nov 10;368(1):91-101
references: 17655903
references: Antiviral Res. 2010 Nov;88(2):227-35
references: 20826184
references: Antiviral Res. 1999 Oct;43(3):145-55
references: 10551373
references: N Engl J Med. 2013 Feb 14;368(7):633-43
references: 23406028
references: J Virol. 2014 Apr;88(8):4229-36
references: 24478430
references: PLoS Pathog. 2008 May 30;4(5):e1000077
references: 18516301
references: Cell. 2012 Feb 3;148(3):421-33
references: 22304913
references: Nat Med. 2001 Jun;7(6):719-24
references: 11385510
references: J Pharmacogenomics Pharmacoproteomics. 2014 Sep 30;5(4):null
references: 25584194
references: J Agric Food Chem. 2004 Nov 17;52(23):7172-9
references: 15537334
references: Cell Signal. 2013 Oct;25(10):1939-48
references: 23770291
references: Molecules. 2011 Feb 28;16(3):2032-52
references: 21358592
references: PLoS Pathog. 2011 Feb 03;7(2):e1001271
references: 21304882
references: World J Gastroenterol. 2010 Jan 14;16(2):184-92
references: 20066737
references: Lancet. 2002 Nov 2;360(9343):1393-4
references: 12423987
references: Am J Pathol. 2013 Nov;183(5):1390-6
references: 24091251
references: J Biol Chem. 2001 Jun 8;276(23):19715-22
references: 11259439
references: Virology. 2008 Apr 25;374(1):114-27
references: 18234263
references: J Allergy Clin Immunol. 2008 Sep;122(3):456-68; quiz 469-70
references: 18774381
references: Inflammation. 2012 Aug;35(4):1392-401
references: 22391746
references: Acta Med Okayama. 1978 Aug;32(4):265-72
references: 153087
references: Antiviral Res. 2006 Dec;72 (3):242-51
references: 16876885
references: J Med Virol. 1985 Jan;15(1):71-9
references: 2981979
references: Methods Mol Biol. 2012;809:105-20
references: 22113271
references: Biol Trace Elem Res. 1997 Jan;56(1):107-16
references: 9152514
references: Mol Cell Biol. 2005 Sep;25(18):7966-75
references: 16135789
references: Chembiochem. 2004 Oct 4;5(10):1348-58
references: 15457532
references: Antiviral Res. 2004 Aug;63(2):85-95
references: 15302137
references: EMBO J. 2004 Jun 16;23(12):2369-80
references: 15152190
references: Mol Cancer Res. 2011 Oct;9(10):1346-55
references: 21856773
references: Am J Respir Crit Care Med. 2011 Jun 1;183(11):1550-60
references: 21471094
references: J Virol. 2005 Aug;79(16):10190-9
references: 16051812
references: Viruses. 2012 Dec 07;4(12):3551-71
references: 23223197
references: Am J Respir Crit Care Med. 2006 Dec 15;174(12 ):1361-9
references: 17008643
references: Clin Infect Dis. 2007 May 1;44(9):1152-8
references: 17407031
references: Nat Rev Drug Discov. 2006 Jun;5(6):493-506
references: 16732220
references: Biochem Soc Trans. 2010 Feb;38(Pt 1):50-3
references: 20074034
references: J Exp Clin Cancer Res. 2009 Jul 01;28:96
references: 19570215
references: Antiviral Res. 2012 Jun;94(3):258-71
references: 22465313
references: Int Rev Cytol. 2004;237:57-89
references: 15380666
references: Clin Microbiol Rev. 2011 Oct;24(4):734-54
references: 21976607
references: Mol Cell. 2008 Mar 14;29(5):539-40
references: 18342601
references: Nucleic Acids Res. 1989 Aug 11;17(15):6419
references: 2771659
references: Nat Rev Mol Cell Biol. 2004 May;5(5):392-401
references: 15122352
references: J Virol. 2011 Dec;85(24):13061-8
references: 21937650
references: Biochimie. 2007 Jan;89(1):73-82
references: 17045724
references: J Infect Dis. 2005 May 15;191(10):1719-29
references: 15838800
references: Am J Hypertens. 2013 Nov;26(11):1260-8
references: 24025725
references: Diabetes. 2011 Dec;60(12):3235-45
references: 22110092
references: Antiviral Res. 2006 Dec;72(3):171-7
references: 16899306
references: PLoS One. 2013 Apr 23;8(4):e62568
references: 23626834
references: J Gen Virol. 2008 Aug;89(Pt 8):1978-86
references: 18632970
references: Inflamm Allergy Drug Targets. 2010 Sep;9(4):263-85
references: 20887269