Hepatitis C virus modulates signal peptide peptidase to alter host protein processing

Author:

Hirano Junki,Yoshio Sachiyo,Sakai Yusuke,Songling Li,Suzuki Tatsuya,Itoh Yumi,Zhang He,Chen David Virya,Haga Saori,Oomori Hiroko,Kodama TakahiroORCID,Maeda Yusuke,Ono Yoshihiro,Takahashi Yu,Standley Daron M.,Yamamoto Masahiro,Moriishi KohjiORCID,Moriya Kyoji,Kanto TatsuyaORCID,Takehara TetsuoORCID,Koike Kazuhiko,Matsuura YoshiharuORCID,Okamoto Toru

Abstract

Immunoevasins are viral proteins that prevent antigen presentation on major histocompatibility complex (MHC) class I, thus evading host immune recognition. Hepatitis C virus (HCV) evades immune surveillance to induce chronic infection; however, how HCV-infected hepatocytes affect immune cells and evade immune recognition remains unclear. Herein, we demonstrate that HCV core protein functions as an immunoevasin. Its expression interfered with the maturation of MHC class I molecules catalyzed by the signal peptide peptidase (SPP) and induced their degradation via HMG-CoA reductase degradation 1 homolog, thereby impairing antigen presentation to CD8+ T cells. The expression of MHC class I in the livers of HCV core transgenic mice and chronic hepatitis C patients was impaired but was restored in patients achieving sustained virological response. Finally, we show that the human cytomegalovirus US2 protein, possessing a transmembrane region structurally similar to the HCV core protein, targets SPP to impair MHC class I molecule expression. Thus, SPP represents a potential target for the impairment of MHC class I molecules by DNA and RNA viruses.

Funder

Japan Agency for Medical Research and Development

Ministry of Education, Culture, Sports, Science and Technology

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Reference57 articles.

1. Natural history of acute and chronic hepatitis C

2. Extrahepatic manifestations of chronic HCV infection;Galossi;J. Gastrointestin. Liver Dis.,2007

3. The Natural History of Hepatitis C Virus (HCV) Infection

4. Innate and adaptive immune responses in HCV infections

5. Direct-acting antiviral medications for chronic hepatitis C virus infection;Jazwinski;Gastroenterol. Hepatol. (N. Y.),2011

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