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Virus Res
. 2021 Feb 10;198337.
doi: 10.1016/j.virusres.2021.198337. Online ahead of print.
TGF-β1 signaling inhibit the in vitro apoptotic, infection and stimulatory cell response induced by influenza H1N1 virus infection on A549 cells
Genoveva Bustos Rivera-Bahena 1 , Alicia Helena M?rquez-Bandala 2 , Delia Vanessa L?pez-Guerrero 3 , Fernando R Esquivel-Guadarrama 2 , Jose-Luis Montiel-Hern?ndez 4
Affiliations
- PMID: 33581185
- DOI: 10.1016/j.virusres.2021.198337
Abstract
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 hour 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 and NS1 proteins 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.
Keywords: IL-1β; Influenza A virus (IAV); M1 viral protein; Smad7; TGF-β1; apoptosis; inflammasome.