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10.1371/journal.ppat.1008062

http://scihub22266oqcxt.onion/10.1371/journal.ppat.1008062
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suck abstract from ncbi


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pmid31585000
      PLoS+Pathog 2019 ; 15 (10 ): e1008062
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  • Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling #MMPMID31585000
  • Wei F ; Jiang Z ; Sun H ; Pu J ; Sun Y ; Wang M ; Tong Q ; Bi Y ; Ma X ; Gao GF ; Liu J
  • PLoS Pathog 2019[Oct]; 15 (10 ): e1008062 PMID31585000 show ga
  • Type I interferons (IFNs) play a critical role in host defense against influenza virus infection, and the mechanism of influenza virus to evade type I IFNs responses remains to be fully understood. Here, we found that progranulin (PGRN) was significantly increased both in vitro and in vivo during influenza virus infection. Using a PGRN knockdown assay and PGRN-deficient mice model, we demonstrated that influenza virus-inducing PGRN negatively regulated type I IFNs production by inhibiting the activation of NF-?B and IRF3 signaling. Furthermore, we showed that PGRN directly interacted with NF-?B essential modulator (NEMO) via its Grn CDE domains. We also verified that PGRN recruited A20 to deubiquitinate K63-linked polyubiquitin chains on NEMO at K264. In addition, we found that macrophage played a major source of PGRN during influenza virus infection, and PGRN neutralizing antibodies could protect against influenza virus-induced lethality in mice. Our data identify a PGRN-mediated IFN evasion pathway exploited by influenza virus with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of PGRN in innate immunity.
  • |Animals [MESH]
  • |Antiviral Agents/*pharmacology [MESH]
  • |Cells, Cultured [MESH]
  • |Down-Regulation [MESH]
  • |Host-Pathogen Interactions [MESH]
  • |Immune Evasion/*immunology [MESH]
  • |Immunity, Innate/*immunology [MESH]
  • |Interferon Type I/*metabolism [MESH]
  • |Male [MESH]
  • |Mice [MESH]
  • |Mice, Knockout [MESH]
  • |NF-kappa B [MESH]
  • |Orthomyxoviridae Infections/*immunology/metabolism/virology [MESH]
  • |Orthomyxoviridae/*immunology [MESH]
  • |Progranulins/*physiology [MESH]


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