Thogoto virus ML protein is a potent inhibitor of the interferon regulatory factor-7 transcription factor.
The tick-transmitted orthomyxovirus Thogoto virus (THOV) encodes the ML protein acting as a viral suppressor of the host interferon (IFN) system. Here, we describe that type I IFN is strongly induced in primary mouse embryo fibroblasts as well as plasmacytoid dendritic cells upon infection with a THOV mutant lacking the ML gene. However, wild-type THOV encoding ML suppresses induction of IFN by preventing the activation of members of the IFN regulatory factor (IRF) family. We found that reporter gene expression dependent on IRF3 and IRF7 was strongly inhibited by ML. Further experiments revealed that ML interacts with IRF7 and prevents dimerization of the transcription factor and its association with the coactivator TRAF6. Interestingly, another IRF7 activation step, nuclear translocation, is not affected by ML. Our data elucidate ML protein as a virulence factor with an IRF-specific IFN-antagonistic spectrum.
Buettner
Nico
N
Abteilung Virologie, Universität Freiburg, D-79008 Freiburg, Germany.
Vogt
Carola
C
Martínez-Sobrido
Luis
L
Weber
Friedemann
F
Waibler
Zoe
Z
Kochs
Georg
G
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D019281:Dimerization; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors; D050839:Interferon Regulatory Factor-7 / Q000037:antagonists & inhibitors*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D025941:Protein Interaction Mapping; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D018117:Thogotovirus / Q000276:immunology* / Q000472:pathogenicity*; D014764:Viral Proteins / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*
D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D048029:TNF Receptor-Associated Factor 6; D014764:Viral Proteins; D037521:Virulence Factors; D007371:Interferon-gamma