Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Virology Journal
Published in: Virology Journal 1/2013

Open Access 01-12-2013 | Research

Transcription factor regulation and cytokine expression following in vitro infection of primary chicken cell culture with low pathogenic avian influenza virus

Authors: Haijun Jiang, Kangzhen Yu, Darrell R Kapczynski

Published in: Virology Journal | Issue 1/2013

Login to get access

Abstract

Background

Avian influenza virus (AIV) induced proinflammatory cytokine expression is believed to contribute to the disease pathogenesis following infection of poultry. However, there is limited information on the avian immune response to infection with low pathogenic avian influenza virus (LPAIV).

Methods

To gain a better understanding of the early viral-host interactions of LPAIV in chickens, primary chicken embryo hepatocytes (CEH) were infected with four different LPAIVs of U.S. origin. Kinetics of virus replication, transcription factor (c-Jun, p50 and IRF-3) activation and immune response gene (IL-6, IL-1beta, IFN-alpha and Mx) expression were studied at four different time points (6, 12, 24 and 48 hours) post infection and compared to non-infected controls.

Results

CEH can support growth of the tested LPAIVs when with trypsin supplementation. All four immune response genes tested were upregulated following infection as were transcription factors c-Jun, p50 and IRF-3. Amplification of these genes was dependant on virus replication (e.g. inclusion of trypsin), such that immune response genes and transcription factors were upregulated as viral titers increased.

Conclusion

The results of these studies demonstrate the requirement of virus replication for innate immune regulation and broaden our understanding of transcription factor responses related to LPAIV infection in chickens.
Appendix
Available only for authorised users
Literature
1.
Kapczynski DR, Liljebjelke K, Kulkarni G, Hunt H, Jiang HJ, Petkov D: Cross reactive cellular immune responses in chickens previously exposed to low pathogenic avian influenza. BMC Proc 2011,5(4):S13.PubMedPubMedCentralCrossRef
2.
Swayne DE, Kapczynski D: Strategies and challenges for eliciting immunity against avian influenza virus in birds. Immunol Rev 2008, 225: 314-331. 10.1111/j.1600-065X.2008.00668.xPubMedCrossRef
3.
Kapczynski DR, Swayne DE: Influenza vaccines for avian species. Curr Top Microbiol Immunol 2009, 333: 133-152.PubMed
4.
Veits J, Weber S, Stech O, Breithaupt A, Graber M, Gohrbandt S, Bogs J, Hundt J, Teifke JP, Mettenleiter TC, Stech J: Avian influenza virus hemagglutinins H2, H4, H8, and H14 support a highly pathogenic phenotype. Proc Natl Acad Sci USA 2012, 109: 2579-2584. 10.1073/pnas.1109397109PubMedPubMedCentralCrossRef
5.
Capua I, Alexander DJ: Avian influenza infections in birds–a moving target. Influenza Other Respi Viruses 2007, 1: 11-18.CrossRef
6.
Capua I, Alexander DJ: Avian influenza: recent developments. Avian Pathol 2004, 33: 393-404. 10.1080/03079450410001724085PubMedCrossRef
7.
Fusaro A, Monne I, Salviato A, Valastro V, Schivo A, Amarin NM, Gonzalez C, Ismail MM, Al-Ankari AR, Al-Blowi MH, et al.: Phylogeography and evolutionary history of reassortant H9N2 viruses with potential human health implications. J Virol 2011, 85: 8413-8421. 10.1128/JVI.00219-11PubMedPubMedCentralCrossRef
8.
Homme PJ, Easterday BC: Avian influenza virus infections: I: Characteristics of influenza A-turkey-Wisconsin-1966 virus. Avian Dis 1970, 14: 66-74. 10.2307/1588557PubMedCrossRef
9.
Soda K, Asakura S, Okamatsu M, Sakoda Y, Kida H: H9N2 influenza virus acquires intravenous pathogenicity on the introduction of a pair of di-basic amino acid residues at the cleavage site of the hemagglutinin and consecutive passages in chickens. Virol J 2011, 8: 64. 10.1186/1743-422X-8-64PubMedPubMedCentralCrossRef
10.
Qiao C, Liu Q, Bawa B, Shen H, Qi W, Chen Y, Mok CK, Garcia-Sastre A, Richt JA, Ma W: Pathogenicity and transmissibility of reassortant H9 influenza viruses with genes from pandemic H1N1 virus. J Gen Virol 2012, 93: 2337-2345. 10.1099/vir.0.044040-0PubMedPubMedCentralCrossRef
11.
Butt KM, Smith GJ, Chen H, Zhang LJ, Leung YH, Xu KM, Lim W, Webster RG, Yuen KY, Peiris JS, Guan Y: Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003. J Clin Microbiol 2005, 43: 5760-5767. 10.1128/JCM.43.11.5760-5767.2005PubMedPubMedCentralCrossRef
12.
Saito T, Lim W, Suzuki T, Suzuki Y, Kida H, Nishimura SI, Tashiro M: Characterization of a human H9N2 influenza virus isolated in Hong Kong. Vaccine 2001, 20: 125-133. 10.1016/S0264-410X(01)00279-1PubMedCrossRef
13.
Maecker H, Varfolomeev E, Kischkel F, Lawrence D, LeBlanc H, Lee W, Hurst S, Danilenko D, Li J, Filvaroff E, et al.: TWEAK attenuates the transition from innate to adaptive immunity. Cell 2005, 123: 931-944. 10.1016/j.cell.2005.09.022PubMedCrossRef
14.
Lowenthal JW, Lambrecht B, van den Berg TP, Andrew ME, Strom AD, Bean AG: Avian cytokines - the natural approach to therapeutics. Dev Comp Immunol 2000, 24: 355-365. 10.1016/S0145-305X(99)00083-XPubMedCrossRef
15.
Jiang H, Yang H, Kapczynski DR: Chicken interferon alpha pretreatment reduces virus replication of pandemic H1N1 and H5N9 avian influenza viruses in lung cell cultures from different avian species. Virol J 2011, 8: 447. 10.1186/1743-422X-8-447PubMedPubMedCentralCrossRef
16.
Meylan E, Tschopp J, Karin M: Intracellular pattern recognition receptors in the host response. Nature 2006, 442: 39-44. 10.1038/nature04946PubMedCrossRef
17.
Janeway CA Jr, Medzhitov R: Innate immune recognition. Annu Rev Immunol 2002, 20: 197-216. 10.1146/annurev.immunol.20.083001.084359PubMedCrossRef
18.
Zhong B, Tien P, Shu HB: Innate immune responses: crosstalk of signaling and regulation of gene transcription. Virology 2006, 352: 14-21. 10.1016/j.virol.2006.04.029PubMedCrossRef
19.
Bowie AG, Unterholzner L: Viral evasion and subversion of pattern-recognition receptor signalling. Nat Rev Immunol 2008, 8: 911-922. 10.1038/nri2436PubMedCrossRef
20.
Bos TJ, Monteclaro FS, Mitsunobu F, Ball AR Jr, Chang CH, Nishimura T, Vogt PK: Efficient transformation of chicken embryo fibroblasts by c-Jun requires structural modification in coding and noncoding sequences. Genes Dev 1990, 4: 1677-1687. 10.1101/gad.4.10.1677PubMedCrossRef
21.
Capobianco AJ, Chang D, Mosialos G, Gilmore TD: p105, the NF-kappa B p50 precursor protein, is one of the cellular proteins complexed with the v-Rel oncoprotein in transformed chicken spleen cells. J Virol 1992, 66: 3758-3767.PubMedPubMedCentral
22.
Grant CE, Vasa MZ, Deeley RG: cIRF-3, a new member of the interferon regulatory factor (IRF) family that is rapidly and transiently induced by dsRNA. Nucleic Acids Res 1995, 23: 2137-2146. 10.1093/nar/23.12.2137PubMedPubMedCentralCrossRef
23.
Saitoh T, Tun-Kyi A, Ryo A, Yamamoto M, Finn G, Fujita T, Akira S, Yamamoto N, Lu KP, Yamaoka S: Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1. Nat Immunol 2006, 7: 598-605. 10.1038/ni1347PubMedCrossRef
24.
Takahasi K, Suzuki NN, Horiuchi M, Mori M, Suhara W, Okabe Y, Fukuhara Y, Terasawa H, Akira S, Fujita T, Inagaki F: X-ray crystal structure of IRF-3 and its functional implications. Nat Struct Biol 2003, 10: 922-927. 10.1038/nsb1001PubMedCrossRef
25.
Kapczynski DR, Pantin-Jackwood M, Guzman SG, Ricardez Y, Spackman E, Bertran K, Suarez DL, Swayne DE: Characterization of the 2012 highly pathogenic avian influenza H7N3 virus isolated from poultry in an outbreak in Mexico: pathobiology and vaccine protection. J Virol 2013, 87: 9086-9096. 10.1128/JVI.00666-13PubMedPubMedCentralCrossRef
26.
Post J, de Geus ED, Vervelde L, Cornelissen JB, Rebel JM: Systemic distribution of different low pathogenic avian influenza (LPAI) viruses in chicken. Virol J 2013, 10: 23. 10.1186/1743-422X-10-23PubMedPubMedCentralCrossRef
27.
van Riel D, van den Brand JM, Munster VJ, Besteboer TM, Fouchier RA, Osterhaus AD, Kuiken T: Pathology and virus distribution in chickens naturally infected with highly pathogenic avian influenza A virus (H7N7) During the 2003 outbreak in The Netherlands. Vet Pathol 2009, 46: 971-976. 10.1354/vp.08-VP-0215-K-BCPubMedCrossRef
28.
Lee J, Foster DN, Bottje WG, Jang HM, Chandra YG, Gentles LE, Kong BW: Establishment of an immortal chicken embryo liver-derived cell line. Poult Sci 2013, 92: 1604-1612. 10.3382/ps.2012-02582PubMedCrossRef
29.
Lukert PD: Immunofluorescence of avian infectious bronchitis virus in primary chicken embryo kidney, liver, lung, and fibroblast cell cultures. Arch Gesamte Virusforsch 1966, 19: 265-272. 10.1007/BF01241849PubMedCrossRef
30.
Allan GM, McNulty MS: A direct immunofluorescence test for the rapid detection of avian influenza virus antigen in tissue impression smears. Avian Pathol 1985, 14: 449-460. 10.1080/03079458508436248PubMedCrossRef
31.
Julkunen I, Sareneva T, Pirhonen J, Ronni T, Melen K, Matikainen S: Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Cytokine Growth Factor Rev 2001, 12: 171-180. 10.1016/S1359-6101(00)00026-5PubMedCrossRef
32.
Kaufmann A, Salentin R, Meyer RG, Bussfeld D, Pauligk C, Fesq H, Hofmann P, Nain M, Gemsa D, Sprenger H: Defense against influenza A virus infection: essential role of the chemokine system. Immunobiology 2001, 204: 603-613. 10.1078/0171-2985-00099PubMedCrossRef
33.
Ma W, Belisle SE, Mosier D, Li X, Stigger-Rosser E, Liu Q, Qiao C, Elder J, Webby R, Katze MG, Richt JA: 2009 pandemic H1N1 influenza virus causes disease and upregulation of genes related to inflammatory and immune responses, cell death, and lipid metabolism in pigs. J Virol 2011, 85: 11626-11637. 10.1128/JVI.05705-11PubMedPubMedCentralCrossRef
34.
Ludwig S, Ehrhardt C, Neumeier ER, Kracht M, Rapp UR, Pleschka S: Influenza virus-induced AP-1-dependent gene expression requires activation of the JNK signaling pathway. J Biol Chem 2001, 276: 10990-10998. 10.1074/jbc.M009902200CrossRef
35.
Bot A, Rodrigo E, Wolfe T, Bot S, Von Herrath MG: Infection-triggered regulatory mechanisms override the role of STAT 4 in control of the immune response to influenza virus antigens. J Virol 2003, 77: 5794-5800. 10.1128/JVI.77.10.5794-5800.2003PubMedPubMedCentralCrossRef
36.
Ronni T, Sareneva T, Pirhonen J, Julkunen I: Activation of IFN-alpha, IFN-gamma, MxA, and IFN regulatory factor 1 genes in influenza A virus-infected human peripheral blood mononuclear cells. J Immunol 1995, 154: 2764-2774.PubMed
37.
Chen J, Lee KH, Steinhauer DA, Stevens DJ, Skehel JJ, Wiley DC: Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation. Cell 1998, 95: 409-417. 10.1016/S0092-8674(00)81771-7PubMedCrossRef
38.
Steinhauer DA: Role of hemagglutinin cleavage for the pathogenicity of influenza virus. Virology 1999, 258: 1-20. 10.1006/viro.1999.9716PubMedCrossRef
39.
Salomon R, Hoffmann E, Webster RG: Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc Natl Acad Sci USA 2007, 104: 12479-12481. 10.1073/pnas.0705289104PubMedPubMedCentralCrossRef
40.
Cameron CM, Cameron MJ, Bermejo-Martin JF, Ran L, Xu L, Turner PV, Ran R, Danesh A, Fang Y, Chan PK, et al.: Gene expression analysis of host innate immune responses during Lethal H5N1 infection in ferrets. J Virol 2008, 82: 11308-11317. 10.1128/JVI.00691-08PubMedPubMedCentralCrossRef
41.
Zheng BJ, Chan KW, Lin YP, Zhao GY, Chan C, Zhang HJ, Chen HL, Wong SS, Lau SK, Woo PC, et al.: Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus. Proc Natl Acad Sci USA 2008, 105: 8091-8096. 10.1073/pnas.0711942105PubMedPubMedCentralCrossRef
42.
Adams SC, Xing Z, Li J, Cardona CJ: Immune-related gene expression in response to H11N9 low pathogenic avian influenza virus infection in chicken and Pekin duck peripheral blood mononuclear cells. Mol Immunol 2009, 46: 1744-1749. 10.1016/j.molimm.2009.01.025PubMedCrossRef
43.
Xing Z, Cardona CJ, Li J, Dao N, Tran T, Andrada J: Modulation of the immune responses in chickens by low-pathogenicity avian influenza virus H9N2. J Gen Virol 2008, 89: 1288-1299. 10.1099/vir.0.83362-0PubMedCrossRef
44.
Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T: IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 2003, 4: 491-496. 10.1038/ni921PubMedCrossRef
45.
Kim MJ, Latham AG, Krug RM: Human influenza viruses activate an interferon-independent transcription of cellular antiviral genes: outcome with influenza A virus is unique. Proc Natl Acad Sci USA 2002, 99: 10096-10101. 10.1073/pnas.152327499PubMedPubMedCentralCrossRef
46.
Zhang B, Li M, Chen L, Yang K, Shan Y, Zhu L, Sun S, Li L, Wang C: The TAK1-JNK cascade is required for IRF3 function in the innate immune response. Cell Res 2009, 19: 412-428. 10.1038/cr.2009.8PubMedCrossRef
47.
Grant CE, May DL, Deeley RG: DNA binding and transcription activation by chicken interferon regulatory factor-3 (chIRF-3). Nucleic Acids Res 2000, 28: 4790-4799. 10.1093/nar/28.23.4790PubMedPubMedCentralCrossRef
48.
May DL, Grant CE, Deeley RG: Cloning and promoter analysis of the chicken interferon regulatory factor-3 gene. DNA Cell Biol 2000, 19: 555-566. 10.1089/104454900439782PubMedCrossRef
49.
Liniger M, Summerfield A, Zimmer G, McCullough KC, Ruggli N: Chicken cells sense influenza A virus infection through MDA5 and CARDIF signaling involving LGP2. J Virol 2012, 86: 705-717. 10.1128/JVI.00742-11PubMedPubMedCentralCrossRef
50.
Flory E, Kunz M, Scheller C, Jassoy C, Stauber R, Rapp UR, Ludwig S: Influenza virus-induced NF-kappaB-dependent gene expression is mediated by overexpression of viral proteins and involves oxidative radicals and activation of IkappaB kinase. J Biol Chem 2000, 275: 8307-8314. 10.1074/jbc.275.12.8307PubMedCrossRef
51.
Pahl HL, Baeuerle PA: Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B. J Virol 1995, 69: 1480-1484.PubMedPubMedCentral
52.
Wang X, Hussain S, Wang EJ, Li MO, Garcia-Sastre A, Beg AA: Lack of essential role of NF-kappa B p50, RelA, and cRel subunits in virus-induced type 1 IFN expression. J Immunol 2007, 178: 6770-6776.PubMedCrossRef
53.
Wei L, Sandbulte MR, Thomas PG, Webby RJ, Homayouni R, Pfeffer LM: NFkappaB negatively regulates interferon-induced gene expression and anti-influenza activity. J Biol Chem 2006, 281: 11678-11684. 10.1074/jbc.M513286200PubMedPubMedCentralCrossRef
54.
Kogut MH, Genovese KJ, He H, Kaiser P: Flagellin and lipopolysaccharide up-regulation of IL-6 and CXCLi2 gene expression in chicken heterophils is mediated by ERK1/2-dependent activation of AP-1 and NF-kappaB signaling pathways. Innate Immun 2008, 14: 213-222. 10.1177/1753425908094416PubMedCrossRef
55.
Kawai T, Akira S: Toll-like receptor and RIG-I-like receptor signaling. Ann N Y Acad Sci 2008, 1143: 1-20. 10.1196/annals.1443.020PubMedCrossRef
56.
Kim TK, Maniatis T: The mechanism of transcriptional synergy of an in vitro assembled interferon-beta enhanceosome. Mol Cell 1997, 1: 119-129. 10.1016/S1097-2765(00)80013-1PubMedCrossRef
57.
Kujime K, Hashimoto S, Gon Y, Shimizu K, Horie T: p38 mitogen-activated protein kinase and c-jun-NH2-terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. J Immunol 2000, 164: 3222-3228.PubMedCrossRef
58.
Takeuchi O, Akira S: MDA5/RIG-I and virus recognition. Curr Opin Immunol 2008, 20: 17-22. 10.1016/j.coi.2008.01.002PubMedCrossRef
59.
Saito T, Owen DM, Jiang F, Marcotrigiano J, Gale M Jr: Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature 2008, 454: 523-527. 10.1038/nature07106PubMedPubMedCentralCrossRef
60.
McNulty MS, Allan GM, Todd D, McFerran JB, McKillop ER, Collins DS, McCracken RM: Isolation of rotaviruses from turkeys and chickens: demonstration of distinct serotypes and RNA electropherotypes. Avian Pathol 1980, 9: 363-375. 10.1080/03079458008418420PubMedCrossRef
61.
Lavrentieva IN, Medvedeva TE, Golubev DB: Characterization of the reproduction of influenza A epidemic viruses in cell cultures. Acta Virol 1986, 30: 137-142.PubMed
62.
Reed LJ, Muench H: A simple method for estimating fifty percent endpoints. American Journal of Hygiene 1938, 27: 493-497.
63.
Kapczynski DR, Kogut MH: Measurement of avian cytokines with real-time RT-PCR following infection with the avian influenza virus. Methods Mol Biol 2008, 436: 127-134.PubMed
64.
Rue CA, Susta L, Cornax I, Brown CC, Kapczynski DR, Suarez DL, King DJ, Miller PJ, Afonso CL: Virulent Newcastle disease virus elicits a strong innate immune response in chickens. J Gen Virol 2011, 92: 931-939. 10.1099/vir.0.025486-0PubMedCrossRef
65.
Morrison TB, Weis JJ, Wittwer CT: Quantification of low-copy transcripts by continuous SYBR Green I monitoring during amplification. Biotechniques 1998, 24: 954-958. 960, 962PubMed
Metadata
Title
Transcription factor regulation and cytokine expression following in vitro infection of primary chicken cell culture with low pathogenic avian influenza virus
Authors
Haijun Jiang
Kangzhen Yu
Darrell R Kapczynski
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-10-342

Other articles of this Issue 1/2013

Virology Journal 1/2013 Go to the issue

Research

No association between XMRV or related gammaretroviruses in Australian prostate cancer patients

Research

Meta-analysis of the short-term effects of lamivudine treatment for severe chronic hepatitis B

Research

Histopathological changes in the liver of tree shrew (Tupaia belangeri chinensis) persistently infected with hepatitis B virus

Research

Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in cervical cancer

Research

Epigenetic regulation of polyomavirus JC

Research

Isolation and analysis of a very virulent Marek’s disease virus strain in China
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits