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Apoptotic and Early Innate Immune Responses to PB1-F2 Protein of Influenza A Viruses Belonging to Different Subtypes in Human Lung Epithelial A549 Cells

Identifieur interne : 000222 ( Main/Exploration ); précédent : 000221; suivant : 000223

Apoptotic and Early Innate Immune Responses to PB1-F2 Protein of Influenza A Viruses Belonging to Different Subtypes in Human Lung Epithelial A549 Cells

Auteurs : Gunisha Pasricha [Inde] ; Sanjay Mukherjee [Inde] ; Alok K. Chakrabarti [Inde]

Source :

RBID : PMC:6330835

Abstract

PB1-F2 is a multifunctional protein and contributes to the pathogenicity of influenza A viruses. PB1-F2 is known to have strain and cell specific functions. In this study we have investigated the apoptotic and inflammatory responses of PB1-F2 protein from influenza viruses of diverse pathogenicities in A549 lung epithelial cells. Overexpression of PB1-F2 resulted in apoptosis and heightened inflammatory response in A549 cells. Comparison revealed that the response varied with each subtype. PB1-F2 protein from highly pathogenic H5N1 virus induced least apoptosis but maximum inflammatory response. Results indicated that apoptosis was mediated through death receptor ligands TNFα and TRAIL via Caspase 8 activation. Significant induction of cytokines/chemokines CXCL10, CCL5, CCL2, IFNα, and IL-6 was noted in A549 cells transfected with PB1-F2 gene construct of 2008 West Bengal H5N1 virus (H5N1-WB). On the contrary, PB1-F2 construct from 2007 highly pathogenic H5N1 isolate (H5N1-M) with truncated N-terminal region did not evoke as exuberant inflammatory response as the other H5N1-WB with full length PB1-F2, signifying the importance of N-terminal region of PB1-F2. Sequence analysis revealed that PB1-F2 proteins derived from different influenza viruses varied at multiple amino acid positions. The secondary structure prediction showed each of the PB1-F2 proteins had distinct helix-loop-helix structure. Thus, our data substantiate the notion that the contribution of PB1-F2 to influenza pathogenicity is greatly strain specific and involves multiple host factors. This data demonstrates that PB1-F2 protein of influenza A virus, when expressed independently is minimally apoptotic and strongly influences the early host response in A549 cells.


Url:
DOI: 10.1155/2018/5057184
PubMed: 30687405
PubMed Central: 6330835


Affiliations:


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Le document en format XML

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<p>PB1-F2 is a multifunctional protein and contributes to the pathogenicity of influenza A viruses. PB1-F2 is known to have strain and cell specific functions. In this study we have investigated the apoptotic and inflammatory responses of PB1-F2 protein from influenza viruses of diverse pathogenicities in A549 lung epithelial cells. Overexpression of PB1-F2 resulted in apoptosis and heightened inflammatory response in A549 cells. Comparison revealed that the response varied with each subtype. PB1-F2 protein from highly pathogenic H5N1 virus induced least apoptosis but maximum inflammatory response. Results indicated that apoptosis was mediated through death receptor ligands TNF
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<analytic>
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<name sortKey="Silke, J" uniqKey="Silke J">J. Silke</name>
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<name sortKey="Mcauley, J" uniqKey="Mcauley J">J. McAuley</name>
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<name sortKey="Deng, Y M" uniqKey="Deng Y">Y.-M. Deng</name>
</author>
<author>
<name sortKey="Gilbertson, B" uniqKey="Gilbertson B">B. Gilbertson</name>
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<author>
<name sortKey="Mackenzie Kludas, C" uniqKey="Mackenzie Kludas C">C. Mackenzie-Kludas</name>
</author>
<author>
<name sortKey="Barr, I" uniqKey="Barr I">I. Barr</name>
</author>
<author>
<name sortKey="Brown, L" uniqKey="Brown L">L. Brown</name>
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<analytic>
<author>
<name sortKey="Tauber, S" uniqKey="Tauber S">S. Tauber</name>
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<name sortKey="Ligertwood, Y" uniqKey="Ligertwood Y">Y. Ligertwood</name>
</author>
<author>
<name sortKey="Quigg Nicol, M" uniqKey="Quigg Nicol M">M. Quigg-Nicol</name>
</author>
<author>
<name sortKey="Dutia, B M" uniqKey="Dutia B">B. M. Dutia</name>
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<name sortKey="Elliott, R M" uniqKey="Elliott R">R. M. Elliott</name>
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<name sortKey="Chakrabarti, Alok K" sort="Chakrabarti, Alok K" uniqKey="Chakrabarti A" first="Alok K." last="Chakrabarti">Alok K. Chakrabarti</name>
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