title: Distinct kinetics and pathways of apoptosis in influenza A and B virus infection.
abstract: Annual influenza epidemics are associated with high incidence and mortality rates, and are an important cause of work absenteeism and productivity losses. For successful replication, influenza viruses have evolved as to counteract and/or take a part on host defense mechanisms. Manipulation of apoptosis is one of such mechanisms that have been subject of attention, particularly in relation to influenza type A viruses over the past years. However, this knowledge has not been extended to include influenza type B viruses. In this study, MDCK-SIAT1 cells were infected with influenza A and B strains and the kinetics and pathways of apoptosis post infection were studied, through LDH measurements, Hoechst dye staining, caspase activity assays and protein expression analysis. The resulting data points to a difference in induction of apoptosis profiles between influenza A and B strains. While influenza A strain induced apoptosis later in the course of infection and mainly by the intrinsic pathway, influenza B strain induced apoptosis early in infection by both intrinsic and extrinsic pathways. Also, data revealed the IκB/NF-κB pathway as the major contributor for the observed differences. The study of the virus-host interactions, particularly those that could have an impact on viral replication, are essential in both influenza A and B viruses, as they will allow the identification of viral/host targets common to both influenza types, which could affect viral replication. This information may prove useful for vaccine and antiviral research.
authors.affiliation: Unidade de Investigação e Desenvolvimento, Departamento de Doenças Infecciosas, Instituto Nacional de Saúde Doutor Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisboa, Portugal; Centro de Patogénese Molecular, Unidade dos Retrovírus e Infecções Associadas, Instituto de Medicina Molecular e Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Santos
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Solá
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Cecilia M P
authors.initials: CM
authors.lastname: Rodrigues
authors.affiliation: Unidade de Investigação e Desenvolvimento, Departamento de Doenças Infecciosas, Instituto Nacional de Saúde Doutor Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisboa, Portugal; Centro de Patogénese Molecular, Unidade dos Retrovírus e Infecções Associadas, Instituto de Medicina Molecular e Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: h.rebelo.andrade@insa.min-saude.pt.
authors.forename: Helena
authors.initials: H
authors.lastname: Rebelo-de-Andrade
mesh_terms: D017209:Apoptosis; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D009981:Influenza B virus / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D007700:Kinetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D016328:NF-kappa B
keywords: Apoptosis; Influenza A and B; IκB/NF-κB pathway; PI3K/Akt pathway