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Published in: Virology Journal 1/2010

Open Access 01-12-2010 | Research

Host gene expression profiling in influenza A virus-infected lung epithelial (A549) cells: a comparative analysis between highly pathogenic and modified H5N1 viruses

Authors: Alok K Chakrabarti, Veena C Vipat, Sanjay Mukherjee, Rashmi Singh, Shailesh D Pawar, Akhilesh C Mishra

Published in: Virology Journal | Issue 1/2010

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Abstract

Background

To understand the molecular mechanism of host responses to highly pathogenic avian influenza virus infection and to get an insight into the means through which virus overcomes host defense mechanism, we studied global gene expression response of human lung carcinoma cells (A549) at early and late stages of infection with highly pathogenic avian Influenza A (H5N1) virus and compared it with a reverse genetics modified recombinant A (H5N1) vaccine virus using microarray platform.

Results

The response was studied at time points 4, 8, 16 and 24 hours post infection (hpi). Gene ontology analysis revealed that the genes affected by both the viruses were qualitatively similar but quantitatively different. Significant differences were observed in the expression of genes involved in apoptosis and immune responses, specifically at 16 hpi.

Conclusion

We conclude that subtle differences in the ability to induce specific host responses like apoptotic mechanism and immune responses make the highly pathogenic viruses more virulent.
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Literature
2.
go back to reference Osterholm Michael T : Preparing for the Next Pandemic. NEJM 2005, 352: 18. 10.1056/NEJMp058068CrossRef Osterholm Michael T : Preparing for the Next Pandemic. NEJM 2005, 352: 18. 10.1056/NEJMp058068CrossRef
3.
go back to reference Thomas JK, Noppenberger J: Avian influenza: A review. Am J Health Syst Pharm 2007, 64: 149-165. 10.2146/ajhp060181PubMedCrossRef Thomas JK, Noppenberger J: Avian influenza: A review. Am J Health Syst Pharm 2007, 64: 149-165. 10.2146/ajhp060181PubMedCrossRef
4.
go back to reference Salomon RR, Franks J, Govorkova EA, Ilyushina NA, Yen H, Hulse-Post DJ, Humberd J, Trichet M, Rehg JE, Webby RJ, Webster RG, Hoffmann E: The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. JEM 2006,203(3):689-697. 10.1084/jem.20051938CrossRef Salomon RR, Franks J, Govorkova EA, Ilyushina NA, Yen H, Hulse-Post DJ, Humberd J, Trichet M, Rehg JE, Webby RJ, Webster RG, Hoffmann E: The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. JEM 2006,203(3):689-697. 10.1084/jem.20051938CrossRef
5.
go back to reference Peiris JS, Cheung CY, Leung CY, Nicholls JM: Innate immune responses to influenza A H5N1: friend or foe? Trends in Immunology 2009,30(12):574-584. 10.1016/j.it.2009.09.004PubMedCrossRef Peiris JS, Cheung CY, Leung CY, Nicholls JM: Innate immune responses to influenza A H5N1: friend or foe? Trends in Immunology 2009,30(12):574-584. 10.1016/j.it.2009.09.004PubMedCrossRef
6.
go back to reference Maines TR, Szretter KJ, Perrone L, Belser JA, Bright RA, Zeng H, Tumpey TM, Katz JM: Pathogenesis of emerging avian influenza viruses in mammals and the host innate immune response. Immunological Reviews 2008,225(1):68-84. 10.1111/j.1600-065X.2008.00690.xPubMedCrossRef Maines TR, Szretter KJ, Perrone L, Belser JA, Bright RA, Zeng H, Tumpey TM, Katz JM: Pathogenesis of emerging avian influenza viruses in mammals and the host innate immune response. Immunological Reviews 2008,225(1):68-84. 10.1111/j.1600-065X.2008.00690.xPubMedCrossRef
7.
go back to reference Us D: Cytokine storm in avian influenza. Mikrobiyol Bul 2008,42(2):365-80.PubMed Us D: Cytokine storm in avian influenza. Mikrobiyol Bul 2008,42(2):365-80.PubMed
8.
go back to reference Reemers SS, Leenen D, Koerkamp MJ, Haarlem D, Haar P, Eden W, Vervelde L: Early host responses to avian influenza A virus are prolonged and enhanced at transcriptional level depending on maturation of the immune system. Mol Immun 2010, 47: 1675-1685. 10.1016/j.molimm.2010.03.008CrossRef Reemers SS, Leenen D, Koerkamp MJ, Haarlem D, Haar P, Eden W, Vervelde L: Early host responses to avian influenza A virus are prolonged and enhanced at transcriptional level depending on maturation of the immune system. Mol Immun 2010, 47: 1675-1685. 10.1016/j.molimm.2010.03.008CrossRef
9.
go back to reference Lee DC, Lau ASY: Avian influenza virus signaling: implications for the disease severity of H5N1 infection. Signal Transduction 2007,7(1):64-80. 10.1002/sita.200600117CrossRef Lee DC, Lau ASY: Avian influenza virus signaling: implications for the disease severity of H5N1 infection. Signal Transduction 2007,7(1):64-80. 10.1002/sita.200600117CrossRef
10.
go back to reference Lee SM, Gardy JL, Cheung CY, Cheung TK, Hui KP, Ip NY, Guan Y, Hancock RE, Peiris JSM: System-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages. PLoS One 2009,4(12):e8072. 10.1371/journal.pone.0008072PubMedPubMedCentralCrossRef Lee SM, Gardy JL, Cheung CY, Cheung TK, Hui KP, Ip NY, Guan Y, Hancock RE, Peiris JSM: System-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages. PLoS One 2009,4(12):e8072. 10.1371/journal.pone.0008072PubMedPubMedCentralCrossRef
11.
go back to reference Cameron CM, Cameron MJ, Bermejo-Martin JF, Ran L, Xu L, Turner PV, Ran R, Danesh A, Fang Y, Chan PM, Mytle N, Sullivan TJ, Collins TL, Johnson MG, Medina JC, Rowe T, Kelvin DJ: Gene Expression Analysis of host innate immune responses during lethal H5N1 infection in ferrets. J Virol 2008,82(22):11308-11317. 10.1128/JVI.00691-08PubMedPubMedCentralCrossRef Cameron CM, Cameron MJ, Bermejo-Martin JF, Ran L, Xu L, Turner PV, Ran R, Danesh A, Fang Y, Chan PM, Mytle N, Sullivan TJ, Collins TL, Johnson MG, Medina JC, Rowe T, Kelvin DJ: Gene Expression Analysis of host innate immune responses during lethal H5N1 infection in ferrets. J Virol 2008,82(22):11308-11317. 10.1128/JVI.00691-08PubMedPubMedCentralCrossRef
12.
go back to reference Matsukura S, Kokubu F, Kubo H, Tomita T, Tokunaga H, Kadukora M, Yamamoto T, Kuroiwa Y, Ohno T, Suzaki H, Adachi M: Expression of RANTES by normal airway epithelial cells after influenza virus A infection. Ann J Respir Cell Mol Biol 1998, 18: 255-264.CrossRef Matsukura S, Kokubu F, Kubo H, Tomita T, Tokunaga H, Kadukora M, Yamamoto T, Kuroiwa Y, Ohno T, Suzaki H, Adachi M: Expression of RANTES by normal airway epithelial cells after influenza virus A infection. Ann J Respir Cell Mol Biol 1998, 18: 255-264.CrossRef
13.
go back to reference Salomon R, Hoffmann E, Webster RG: Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. PNAS 2007,104(30):12479-12481. 10.1073/pnas.0705289104PubMedPubMedCentralCrossRef Salomon R, Hoffmann E, Webster RG: Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. PNAS 2007,104(30):12479-12481. 10.1073/pnas.0705289104PubMedPubMedCentralCrossRef
14.
go back to reference Nicholls JM, Chan MC, Chan WY, Wong HK, Cheung CY, et al.: Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. Nat Med 2007, 13: 147-149. 10.1038/nm1529PubMedCrossRef Nicholls JM, Chan MC, Chan WY, Wong HK, Cheung CY, et al.: Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. Nat Med 2007, 13: 147-149. 10.1038/nm1529PubMedCrossRef
15.
go back to reference Chakrabarti AK, Pawar SD, Cherian SS, Koratkar SS, Jadhav SM, Pal B, Raut S, Thite V, Kode SS, Keng SS, Payyapilly BJ, Mullick J, Mishra AC: Characterization of the Influenza A H5N1 Viruses of the 2008-09 Outbreaks in India reveals a third introduction and possible endemicity. PLoS One 2009,4(11):e7846. 10.1371/journal.pone.0007846PubMedPubMedCentralCrossRef Chakrabarti AK, Pawar SD, Cherian SS, Koratkar SS, Jadhav SM, Pal B, Raut S, Thite V, Kode SS, Keng SS, Payyapilly BJ, Mullick J, Mishra AC: Characterization of the Influenza A H5N1 Viruses of the 2008-09 Outbreaks in India reveals a third introduction and possible endemicity. PLoS One 2009,4(11):e7846. 10.1371/journal.pone.0007846PubMedPubMedCentralCrossRef
17.
go back to reference Steel J, Lowen AC, Pena L, Angel M, Solo'rzano A, Albrecht R, Perez DR, García-Sastre A, Palese P: Live Attenuated Influenza Viruses Containing NS1 Truncations as Vaccine Candidates against H5N1 Highly Pathogenic Avian Influenza. J Virology 2009,83(4):1742-1753. 10.1128/JVI.01920-08PubMedPubMedCentralCrossRef Steel J, Lowen AC, Pena L, Angel M, Solo'rzano A, Albrecht R, Perez DR, García-Sastre A, Palese P: Live Attenuated Influenza Viruses Containing NS1 Truncations as Vaccine Candidates against H5N1 Highly Pathogenic Avian Influenza. J Virology 2009,83(4):1742-1753. 10.1128/JVI.01920-08PubMedPubMedCentralCrossRef
18.
go back to reference Chan MCW, Cheung CY, Chui WH, Tsao SW, Nicholls JM, Chan YO, Chan RWY, Long HT, Poon LLM, Guan Y, Peiris JM: Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respiratory Research 2005, 6: 135-137. 10.1186/1465-9921-6-135PubMedPubMedCentralCrossRef Chan MCW, Cheung CY, Chui WH, Tsao SW, Nicholls JM, Chan YO, Chan RWY, Long HT, Poon LLM, Guan Y, Peiris JM: Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respiratory Research 2005, 6: 135-137. 10.1186/1465-9921-6-135PubMedPubMedCentralCrossRef
19.
go back to reference Kash JC, Basler CF, García-Sastre A, Carter V, Billharz R, Swayne DE, Ronald M, Przygodzki RM, Jeffery K, Taubenberger JK, Katze MG, Tumpey TM: Global Host Immune Response: Pathogenesis and Transcriptional Profiling of Type A Influenza Viruses Expressing the Hemagglutinin and Neuraminidase Genes from the 1918 Pandemic Virus. J Virology 2004,78(17):9499-9511. 10.1128/JVI.78.17.9499-9511.2004PubMedPubMedCentralCrossRef Kash JC, Basler CF, García-Sastre A, Carter V, Billharz R, Swayne DE, Ronald M, Przygodzki RM, Jeffery K, Taubenberger JK, Katze MG, Tumpey TM: Global Host Immune Response: Pathogenesis and Transcriptional Profiling of Type A Influenza Viruses Expressing the Hemagglutinin and Neuraminidase Genes from the 1918 Pandemic Virus. J Virology 2004,78(17):9499-9511. 10.1128/JVI.78.17.9499-9511.2004PubMedPubMedCentralCrossRef
20.
go back to reference Seo JY, Kim DY, Lee YS, Ro JY: Cytokine production through PKC/p38 signaling pathways, not through JAK/STAT1 pathway, in mast cells stimulated with IFN gamma. Cytokine 2009,46(1):51-60. 10.1016/j.cyto.2008.12.008PubMedCrossRef Seo JY, Kim DY, Lee YS, Ro JY: Cytokine production through PKC/p38 signaling pathways, not through JAK/STAT1 pathway, in mast cells stimulated with IFN gamma. Cytokine 2009,46(1):51-60. 10.1016/j.cyto.2008.12.008PubMedCrossRef
21.
go back to reference Huang Y, Walstrom A, Zhang L, Zhao Y, Cui M, Ye L, Zheng JC: Type I interferons and interferon regulatory factors regulate TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected macrophages. PLoS One 2009,4(4):e5397. 10.1371/journal.pone.0005397PubMedPubMedCentralCrossRef Huang Y, Walstrom A, Zhang L, Zhao Y, Cui M, Ye L, Zheng JC: Type I interferons and interferon regulatory factors regulate TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected macrophages. PLoS One 2009,4(4):e5397. 10.1371/journal.pone.0005397PubMedPubMedCentralCrossRef
22.
go back to reference Schmolke M, Dorothee Viemann D, Johannes Roth J, Ludwig S: Essential Impact of NF-kappaB Signaling on the H5N1 Influenza A Virus-Induced Transcriptome. J Immunol 2009, 183: 5180-5189. 10.4049/jimmunol.0804198PubMedCrossRef Schmolke M, Dorothee Viemann D, Johannes Roth J, Ludwig S: Essential Impact of NF-kappaB Signaling on the H5N1 Influenza A Virus-Induced Transcriptome. J Immunol 2009, 183: 5180-5189. 10.4049/jimmunol.0804198PubMedCrossRef
23.
go back to reference Konig R, Stertz S, Zhou Y, Inoue A, Hoffmann H, Bhattacharyya S, Alamares JG, Tscherne DM, Ortigoza MB, Liang Y, Gao Q, Andrews S, Bandyopadhyay S, Jesus PD, Tu BP, et al.: Human host factors required for influenza virus replication. Nature 2009,463(11):813-17. Konig R, Stertz S, Zhou Y, Inoue A, Hoffmann H, Bhattacharyya S, Alamares JG, Tscherne DM, Ortigoza MB, Liang Y, Gao Q, Andrews S, Bandyopadhyay S, Jesus PD, Tu BP, et al.: Human host factors required for influenza virus replication. Nature 2009,463(11):813-17.
24.
go back to reference Baskin CR, Bielefeldt-Ohmann H, Tumpey TM, Sabourin PJ, Long JP, et al.: Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc Natl Acad Sci USA 2009, 106: 3455-3460. 10.1073/pnas.0813234106PubMedPubMedCentralCrossRef Baskin CR, Bielefeldt-Ohmann H, Tumpey TM, Sabourin PJ, Long JP, et al.: Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc Natl Acad Sci USA 2009, 106: 3455-3460. 10.1073/pnas.0813234106PubMedPubMedCentralCrossRef
25.
go back to reference Zhang C, Yang Y, Zhou X, Liu X, Song H, He Y, Huang P: Highly pathogenic avian influenza A virus H5N1 NS1 protein induces caspase-dependent apoptosis in human alveolar basal epithelial cells. Virology Journal 2010, 7: 51-54. 10.1186/1743-422X-7-51PubMedPubMedCentralCrossRef Zhang C, Yang Y, Zhou X, Liu X, Song H, He Y, Huang P: Highly pathogenic avian influenza A virus H5N1 NS1 protein induces caspase-dependent apoptosis in human alveolar basal epithelial cells. Virology Journal 2010, 7: 51-54. 10.1186/1743-422X-7-51PubMedPubMedCentralCrossRef
26.
go back to reference Uiprasertkul M, Kitphati R, Puthavathana P, Kriwong R, Kongchanagul A, Ungchusak K, Angkasekwinai S, Chokephaibulkit K, Srisook K, Vanprapar N, Auewarakul P: Apoptosis and Pathogenesis of Avian Influenza A (H5N1) Virus in Humans. Emerging Infectious diseases online 2007,13(5):708-712. [http://www.cdc.gov/eid]CrossRef Uiprasertkul M, Kitphati R, Puthavathana P, Kriwong R, Kongchanagul A, Ungchusak K, Angkasekwinai S, Chokephaibulkit K, Srisook K, Vanprapar N, Auewarakul P: Apoptosis and Pathogenesis of Avian Influenza A (H5N1) Virus in Humans. Emerging Infectious diseases online 2007,13(5):708-712. [http://​www.​cdc.​gov/​eid]CrossRef
Metadata
Title
Host gene expression profiling in influenza A virus-infected lung epithelial (A549) cells: a comparative analysis between highly pathogenic and modified H5N1 viruses
Authors
Alok K Chakrabarti
Veena C Vipat
Sanjay Mukherjee
Rashmi Singh
Shailesh D Pawar
Akhilesh C Mishra
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2010
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-7-219

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