TGF-β1 signaling inhibit the in vitro apoptotic, infection and stimulatory cell response induced by influenza H1N1 virus infection on A549 cells

• Published in: Virus research 2021-05, Vol.297, p.198337-198337, Article 198337
• Main Authors: BustosRivera-Bahena, Genoveva, López-Guerrero, Delia Vanessa, Márquez-Bandala, Alicia Helena, Esquivel-Guadarrama, Fernando R., Montiel-Hernández, Jose-Luis
• Format: Article
• Language: English
• Subjects: A549 Cells; Apoptosis; Humans; IL-1β; Inflammasome; Influenza A virus (IAV); Influenza A Virus, H1N1 Subtype; Influenza, Human - immunology; M1 viral protein; Signal Transduction; Smad7; TGF-β1; Transforming Growth Factor beta1 - pharmacology
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2021.198337

•TGF-β1 activation prior to in vitro H1N1 infection blocks cell apoptosis and inflammasome activation.•TGF-β1 activation prior to in vitro H1N1 infection partially inhibits the viral replicative cycle and synthesis of M1 protein.•In vitro H1N1 infection concur with the increase in Smad-7, while this was inhibited by the pre-treatment with TGF-β1. Influenza A virus (IAV) infection induces host cell responses that could derive in inflammatory and apoptotic response. In this respect, in multiple pathological situations, TGF-β1 has shown anti-inflammatory effect, but its role during IAV infection is poorly understood. Interestingly, recent profiling expression studies have suggested that the TGF-β1 pathway could be functionally related to the IAV infection’s host response. To gain an understanding of the involvement of TGF-β1′s signaling pathway during IAV infection, we compared different apoptotic proteins such as TNFR1, Fas ligand, XIAP, cIAP, among others proteins, and pro-inflammatory elements like IL-1β in the A549 cells during IAV infection (H1N1/NC/99), with and without 1 h of pre-treatment with TGF-β1. Pre-incubation with TGF-β1 significantly inhibited apoptosis and the presence of pro-apoptotic factors. Moreover, the relative abundance of immunodetected IAV M1 protein along 24 -h post-infection period was abridged, which correlated with a disminished infectious viral progeny Additionally, caspase 1 activation and increase of IL-1β induced by IAV infection was also reduced by TGF-β1 signaling activation. Whereas IAV infection increase of Smad-7 and, as consequence, partially inhibiting Smad2/3 phosphorylation, pre-treatment with TGF-β1 blocked IAV-dependent Smad7 induction and prevented Smad2/3 signaling shutdown. All these data suggest the role of TGF-β1 signaling pathway in the control of host cell response induced by the IAV infection and identify a potential clinical target to modulate acute cell death.