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

الملخص EN

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.