title: Negative regulation of IRF7 activation by activating transcription factor 4 suggests a cross-regulation between the IFN responses and the cellular integrated stress responses.
abstract: Cells react to viral infection by exhibiting IFN-based innate immune responses and integrated stress responses, but little is known about the interrelationships between the two. In this study, we report a linkage between these two host-protective cellular mechanisms. We found that IFN regulatory factor (IRF)7, the master regulator of type I IFN gene expression, interacts with activating transcription factor (ATF)4, a key component of the integrated stress responses whose translation is induced by viral infection and various stresses. We have demonstrated that IRF7 upregulates ATF4 activity and expression, whereas ATF4 in return inhibits IRF7 activation, suggesting a cross-regulation between the IFN response and the cellular integrated stress response that controls host innate immune defense against viral infection.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liang
authors.forename: Hongying
authors.initials: H
authors.lastname: Deng
authors.forename: Chiao-Wang
authors.initials: CW
authors.lastname: Sun
authors.forename: Tim M
authors.initials: TM
authors.lastname: Townes
authors.forename: Fanxiu
authors.initials: F
authors.lastname: Zhu
mesh_terms: D051701:Activating Transcription Factor 4 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015536:Down-Regulation / Q000276:immunology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007372:Interferons / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D013312:Stress, Physiological / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
chemical_list: C497109:ATF4 protein, human; C081452:Atf4 protein, mouse; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D051701:Activating Transcription Factor 4; D007372:Interferons