title: Deficiency in either 4E-BP1 or 4E-BP2 augments innate antiviral immune responses.
abstract: Genetic deletion of both 4E-BP1 and 4E-BP2 was found to protect cells against viral infections. Here we demonstrate that the individual loss of either 4E-BP1 or 4E-BP2 in mouse embryonic fibroblasts (MEFs) is sufficient to confer viral resistance. shRNA-mediated silencing of 4E-BP1 or 4E-BP2 renders MEFs resistant to viruses, and compared to wild type cells, MEFs knockout for either 4E-BP1 or 4E-BP2 exhibit enhanced translation of Irf-7 and consequently increased innate immune response to viruses. Accordingly, the replication of vesicular stomatitis virus, encephalomyocarditis virus, influenza virus and Sindbis virus is markedly suppressed in these cells. Importantly, expression of either 4E-BP1 or 4E-BP2 in double knockout or respective single knockout cells diminishes their resistance to viral infection. Our data show that loss of 4E-BP1 or 4E-BP2 potentiates innate antiviral immunity. These results provide further evidence for translational control of innate immunity and support targeting translational effectors as an antiviral strategy.
authors.affiliation: Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec H3A 1A3, Canada; College of medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, National Guard Health Affairs, P.O. Box 22490, Riyadh 11426, Mail Code 1515, Saudi Arabia.
authors.forename: Atef
authors.initials: A
authors.lastname: Nehdi
authors.affiliation: Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Polen
authors.initials: P
authors.lastname: Sean
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Izzar
authors.initials: I
authors.lastname: Linares
authors.affiliation: Universidad de la República, Laboratorio de Virología Molecular-PDU, Regional Norte Rivera 1350, CP 50000, Salto, Uruguay.
authors.forename: Rodney
authors.initials: R
authors.lastname: Colina
authors.affiliation: INRS Institut Armand-Frappier Research Centre, 531, boulevard des Prairies, Laval, Quebec, Canada.
authors.forename: Maritza
authors.initials: M
authors.lastname: Jaramillo
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Tommy
authors.initials: T
authors.lastname: Alain
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004686:Encephalomyocarditis virus / Q000502:physiology; D039642:Eukaryotic Initiation Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D051379:Mice; D009975:Orthomyxoviridae / Q000502:physiology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012845:Sindbis Virus / Q000502:physiology; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014779:Virus Replication
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016207:Cytokines; C499527:Eif4ebp1 protein, mouse; C491255:Eif4ebp2 protein, mouse; D039642:Eukaryotic Initiation Factors; D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins