title: p53 serves as a host antiviral factor that enhances innate and adaptive immune responses to influenza A virus.
abstract: Several direct target genes of the p53 tumor suppressor have been identified within pathways involved in viral sensing, cytokine production, and inflammation, suggesting a potential role of p53 in antiviral immunity. The increasing need to identify immune factors to devise host-targeted therapies against pandemic influenza A virus (IAV) led us to investigate the role of endogenous wild-type p53 on the immune response to IAV. We observed that the absence of p53 resulted in delayed cytokine and antiviral gene responses in lung and bone marrow, decreased dendritic cell activation, and reduced IAV-specific CD8(+) T cell immunity. Consequently, p53(-/-) mice showed a more severe IAV-induced disease compared with their wild-type counterparts. These findings establish that p53 influences the antiviral response to IAV, affecting both innate and adaptive immunity. Thus, in addition to its established functions as a tumor suppressor gene, p53 serves as an IAV host antiviral factor that might be modulated to improve anti-IAV therapy and vaccines.
authors: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors: César
authors: C
authors: Muñoz-Fontela
authors: Michael
authors: M
authors: Pazos
authors: Igotz
authors: I
authors: Delgado
authors: William
authors: W
authors: Murk
authors: Sathish Kumar
authors: SK
authors: Mungamuri
authors: Sam W
authors: SW
authors: Lee
authors: Adolfo
authors: A
authors: García-Sastre
authors: Thomas M
authors: TM
authors: Moran
authors: Stuart A
authors: SA
authors: Aaronson
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011024:Pneumonia, Viral / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins