Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 116, Issue 11, Pages 3006-3014Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI29832
Keywords
-
Categories
Funding
- Intramural NIH HHS Funding Source: Medline
- NCI NIH HHS [R01 CA085883, CA85883-01] Funding Source: Medline
Ask authors/readers for more resources
IFN-gamma is known as the initial and primary inducer of immunoproteasomes during viral infections. We now report that type IIFN induced the transcription and translation of immunoproteasome subunits, their incorporation into the proteasome complex, and the generation of an immunoproteasome-dependent CD8 T cell epitope in vitro and provide in vivo evidence that this mechanism occurs prior to IFN-gamma responses at the site of viral infection. Type I IFN-mediated generation of immunoproteasomes was initiated by either poly(I:C) or HCV RNA in human hepatoma cells and was inhibited by neutralization of type IIFN. In serial liver biopsies of chimpanzees with acute HCV infection, increases in immunoproteasome subunit mRNA preceded intrahepatic IFN-gamma responses by several weeks, instead coinciding with intrahepatic type IIFN responses. Thus, viral RNA-induced innate immune responses regulate the antigen-processing machinery, which occurs prior to the detection of IFN-gamma at the site of infection. This mechanism may contribute to the high effectiveness (95%) of type IIFN-based therapies if administered early during HCV infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available