Virus-induced type I IFN stimulates generation of immunoproteasomes at the site of infection

Shin, E. C. et al., J. Clin. Invest., 116:3006-3014 (2006)

Speaker：林雅葶                                                 Date：2007/03/14, 14:10~15:00

Commentator：蕭璦莉 老師                             Place：Room 601

Abstract:

  The immunoproteasome, 26S proteasome, is a major cytosolic antigen-processing complex in many cells. It can generate the most viral peptides form the viral proteins and larger polypeptides in the infected cells¹. CD8 T cells migrate to the infected organ, where they recognize and lyse infected cells that display viral peptides in the context of MHC class I molecules. The levels of IFNs usually increase in the viral infected cells, and IFN-γ is known as the initial and primary inducer of immunoproteasomes during viral infection. The authors now report that type I IFN induce the transcription and translation of immunoproteasome subunits and exhibit the typical structure and function of IFN-γ-inducedimmunoproteasomes in Huh-7 cells. Type I IFN-mediated generation of immunoproteasome was initiated by either poly(I:C) or HCV RNA in Huh-7 cells and was inhibited by neutralization of anti-type I IFN antibodies. In chimpanzees were infected with HCV, the intrahepatic induction of immunoproteasomes precedes the intrahepatic expression of IFN-γ, but coinciding with intrahepatic Type I IFN response³. The present study demonstrates the role of type I IFN in the induction of functional immunoproteasomes in the target organ for the CD8 T cell response during viral infection. Thus, the innate type I IFN response not only exerts antiviral functions but also prepares the infected target organ for the adaptive immune response, in particular by immunoproteasome-dependent antigen processing.

References:

1.          Kloetzel, P.M. Antigen processing by the proteasome. Nat. Rev. Mol. Cell Biol., 2:179–187 (2001).

2.          Rehermann, B. et al., Immunology of hepatitis B virus and hepatitis C virus infection. Nat. Rev. Immunol., 5:215–229 (2005).

3.          Shin, E. C. et al., Virus-induced type I IFN stimulates generation of immunoproteasomes at the site of infection. J. Clin. Invest., 116:3006-3014 (2006).