title: Novel pandemic influenza A (H1N1) virus infection modulates apoptotic pathways that impact its replication in A549 cells.
abstract: It is not well-known whether apoptosis signaling affects influenza virus infection and reproduction in human lung epithelial cells. Using A549 cell line, we studied the relationship of some apoptosis-associated molecules with novel pandemic influenza A (H1N1) virus, A/California/04/2009. Infected cells displayed upregulated Fas ligand, activated FADD and caspase-8, and downregulated FLIP in the extrinsic apoptotic pathway. p53 expression increased and Bcl-XL expression decreased in the intrinsic pathway. Expression of pre-apoptotic molecules (FasL, FADD, and p53) increased virus replication, while inhibition of activity of FADD, caspase-8 and caspase-3, and expression of anti-apoptotic proteins (FLIP and Bcl-XL) decreased virus replication. p38, ERK and JNK from MAPK pathways were activated in infected cells, and inhibition with their inhibitors diminished virus replication. In the p38 superfamily, p38α expression increased viral RNA production, while expression of p38β and p38γ decreased. These data indicated that influenza virus induces apoptotic signaling pathways, which benefit virus replication.
authors.affiliation: Lab of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Bethesda, MD 20892, USA. Electronic address: xue.wang@fda.hhs.gov.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Lab of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Bethesda, MD 20892, USA.
authors.forename: Jiying
authors.initials: J
authors.lastname: Tan
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Zoueva
authors.affiliation: Lab of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Bethesda, MD 20892, USA.
authors.forename: Jiangqin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Lab of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Bethesda, MD 20892, USA.
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases
keywords: Apoptosis; Bax; Fas; MAPK; Pandemic influenza A (H1N1) virus; Viral replication