Hepatitis C virus-induced prion protein expression facilitates hepatitis C virus replication
- 116 Downloads
Hepatitis C virus (HCV) infects approximately 180 million people worldwide. Significant progress has been made since the establishment of in vitro HCV infection models in cells. However, the replication of HCV is complex and not completely understood. Here, we found that the expression of host prion protein (PrP) was induced in an HCV replication cell model. We then showed that increased PrP expression facilitated HCV genomic replication. Finally, we demonstrated that the KKRPK motif on the N-terminus of PrP bound nucleic acids and facilitated HCV genomic replication. Our results provided important insights into how viruses may harness cellular protein to achieve propagation.
Keywordshepatitis C virus (HCV) NS3 NS5B prion protein (PrP)
This work was supported by the Strategic Priority Research Program A of the Chinese Academy of Sciences (XDA12010309), the National Science Foundation of China (31670170), the Nature Science Foundation of Hubei Province (2015CFA087), and the National Basic Research Priorities Program of China (2013CB911102). We thank the Core Facility and Technical Support, Wuhan Institute of Virology for assistance with confocal micros copy (Dr. Ding Gao) and flow cytometry (Ms. Juan Min).
CYL and HXZ designed the study, HXZ performed experiments. CYL, HXZ, SSG, RJP, XWC, analyzed the data. CYL and HXZ wrote the paper.
Compliance with Ethics Guidelines
The authors declare no competing financial interests. This article does not contain any studies with human or animal subjects.
- Kwo P, Gane EJ, Peng C-Y, Pearlman B, Vierling JM, Serfaty L, Buti M, Shafran S, Stryszak P, Lin L. 2017. Effectiveness of elbasvir and grazoprevir combination, with or without ribavirin, for treatment-experienced patients with chronic hepatitis C infection. Gastroenterology, 152: 164–175.PubMedGoogle Scholar
- Nikles D, Bach P, Boller K, Merten CA, Montrasio F, Heppner FL, Aguzzi A, Cichutek K, Kalinke U, Buchholz CJ. 2005. Circumventing tolerance to the prion protein (PrP): Vaccination with PrP-displaying retrovirus particles induces humoral immune responses against the native form of cellular PrP. J Virol, 79: 4033–4042.PubMedPubMedCentralGoogle Scholar
- Yang L, Gao Z, Hu L, Wu G, Yang X, Zhang L, Zhu Y, Wong BS, Xin W, Sy MS. 2016. Glycosylphosphatidylinositol anchor modification machinery deficiency is responsible for the formation of pro-prion protein (PrP) in Bxpc-3 protein and increases cancer cell motility. J Biol Chem, 291: 3905–3917.PubMedGoogle Scholar
- Yang X, Zhang Y, Zhang L, He T, Zhang J, Li C. 2014. Prion protein and cancers. Acta Biochim Biophys Sin (Shanghai), 46: 431–440.Google Scholar