Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling.
Understanding, treating, and preventing diseases caused by immunosuppression and/or persistent infections remain both a major challenge in biomedical research and an important health goal. For a virus or any infectious agent to persist, it must utilize strategies to suppress or evade the host's immune response. Here, we report that two dissimilar viruses employ a common maneuver to cause a profound immunosuppression. Measles virus (MV) and lymphocytic choriomeningitis virus (LCMV) interfere with dendritic cell (DC) development and expansion in vivo and in vitro. The underlying mechanism for this is through the generation of type I interferon (IFN) that acts via a signal transducer and activator of a transcription (STAT)2-dependent, but STAT1-independent, pathway. Thus, viruses subvert the known antiviral effect of type I IFN through STAT2-specific signaling to benefit their survival. These observations have implications for understanding and developing therapies to treat diseases caused by immunosuppression and/or persistent infections.
Hahm
Bumsuk
B
Division of Virology, Department of Neuropharmacology, Department of Infectology , The Scripps Research Institute, La Jolla, California 92037, USA.
Trifilo
Matthew J
MJ
Zuniga
Elina I
EI
Oldstone
Michael B A
MB
D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000502:physiology*; D008459:Measles virus / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018184:Paramyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C494080:Stat1 protein, mouse; C494085:Stat2 protein, mouse; D015534:Trans-Activators