DOI QR코드

DOI QR Code

The Interaction between HCV-Infected huh7.5 Cells and HCV-Specific T Cells

C형 간염 바이러스 감염 간암 세포주와 T 림프구의 상호작용에 대한 연구

  • Kang, Hyojeung (Department of Pharmacy, College of Pharmacy, Kyungpook National University) ;
  • Cho, Hyosun (Department of Pharmacy, College of Pharmacy, Duksung Women's University)
  • 강효정 (경북대학교 약학대학 약학과) ;
  • 조효선 (덕성여자대학교 약학대학 약학과)
  • Received : 2014.03.28
  • Accepted : 2014.05.30
  • Published : 2014.06.30

Abstract

Recently, Hepatitis C virus (HCV) replication system has been established using human hepatoma cells (huh cell) and a variety of HCV clones. In this study, we established an infectious HCV replication system using huh7.5 cells and J6/JFH1 clone (genotype 2a). In addition, we investigated the antigen presentation capability of HCV-infected huh7.5 cells to HCV-specific T cells. Interestingly, HCV-infected huh7.5 cells were not capable of activating HCV-specific T cells. However, huh7.5 cells stimulated by exogenous HCV peptide were able to activate HCV-specific T cells, which was shown to produce TNF-${\alpha}$ and IFN-${\gamma}$. We further examined if HCV infection has an inhibitory effect on the expression of MHC class I molecule of huh7.5 cells. We found that HCV infection did not change the expression level of MHC class I molecule on huh7.5 cells.

최근 인간 간암세포주(human hepatoma cells)를 이용하여 C형 간염 바이러스(hepatitis C virus, HCV)의 복제가 가능한 세포배양모델(cell culture system)이 확립되었다. 본 연구에서는 인간 간암세포주 중 huh7.5 cell (human hepatoma 7.5 cells)과 C형 간염 바이러스인 J6/JFH1 clone (2a 유전자형)를 이용하여 감염 가능한 세포배양모델을 확립하였다. 또한, HCV 감염 간암세포주의 HCV 특이 T 림프구에 대한 항원제시(antigen presentation) 가능성을 살펴보았다. 외부에서 전달된 HCV 항원일 경우 간암세포주의 HCV 특이 T 림프구에 대한 항원제시로 T 림프구의 활성이 가능하였으나, HCV 감염 간암세포주의 경우 T 림프구의 활성을 억제하였다. 이러한 HCV 특이 T 림프구의 활성억제와 HCV 감염 간암세포주 항원제시능의 상관성을 알아보기 위해 HCV 감염 간암세포주의 주조직적합성복합체(major histocompatibility complex, MHC) 발현변화를 측정하였으나 HCV 감염은 간암세포주의 MHC 발현변화에 영향을 미치지 않았다.

Keywords

References

  1. Binder, M., Kochs, G., Bartenschlager, R., and Lohmann, V. 2007. Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy. Hepatology 46, 1365-1374. https://doi.org/10.1002/hep.21829
  2. Cho, H. 2011. The activation of HCV-specific CD8 T cells by HCV peptide pulsed Huh7.5 cells. Korean J. Microbiol. 47, 342-347.
  3. Juandy, J., Aichele, U., Kersting, N., Klein, R., Aichele, P., Bisse, E., Sewell, A.K., Blum, H.E., Bartenschlager, R., Lohmann, V., and et al. 2009. Analysis of CD8+ T-cell-mediated inhibition of hepatitis C virus replication using a novel immunological model. Gastroenterology 136, 1391-1401. https://doi.org/10.1053/j.gastro.2008.12.034
  4. Keril, J.B., McKeating, A.J., and Rice, M.C. 2002. Highly permissive cell lines for subgenomic and genomic hepatitis C Virus RNA replication J. Virol. 76, 13001-13014. https://doi.org/10.1128/JVI.76.24.13001-13014.2002
  5. Kim, B.S. and Park, Y.M. 1993. Prevalence of hepatitis C virus related to liver diseases in Korea. Gastroenterol. Jpn 28, (suppl5) 17S-22S. https://doi.org/10.1007/BF02989198
  6. Lauer, G.M. and Walker, B.D. 2001. Hepatitis C virus infection. New Engl. J. Med. 345, 41-52. https://doi.org/10.1056/NEJM200107053450107
  7. Liang, T.J., Rehermann, B., Seeff, L.B., and Hoofnagle, J.H. 2000. Pathogenesis natural history, treatment, and prevention of hepatitis C. Ann. Intern. Med. 132, 296-305. https://doi.org/10.7326/0003-4819-132-4-200002150-00008
  8. Nakamoto, N., Cho, H., Shaked, A., Olthoff, K., Valiga, M.E., Kaminski, M., Gostick, E., Price, D.A., Freeman, G.J., Wherry, E.J., and Chang, K.M. 2009. Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade. PLoS Pathog. 5, e1000313. https://doi.org/10.1371/journal.ppat.1000313
  9. Nakamoto, N., Kaplan, D.E., Coleclough, J., Li, Y., Valiga, M.E., and Chang, K.M. 2008. Functional restoration of HCV-specific CD8 T cells by PD-1 blockade is defined by PD-1 expression and compartmentalization. Gastroenterology 134, 1927-1937. https://doi.org/10.1053/j.gastro.2008.02.033
  10. Varela-Rohena, A., Carpenito, C., Perez, E.E., Richardson, M., Parry, R.V., Milone, M., Scholler, J., Hao, X., Mexas, A., Carroll, R.G., and et al. 2008. Genetic engineering of T cells for adoptive immunotherapy. Immunol. Res. 42, 166-181. https://doi.org/10.1007/s12026-008-8057-6
  11. Wakita, T., Pietschmann, T., Kato, T., Date, T., Miyamoto, T., Zhao, Z., Murthy, K., Habermann, A., Krausslich, H.G., Mizokami, M., and et al. 2005. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med. 11, 791-796. https://doi.org/10.1038/nm1268
  12. Yi, M. and Lemon, S.M. 2009. Genotype 1a HCV (H77S) infection system. Methods Mol. Biol. 510, 337-346. https://doi.org/10.1007/978-1-59745-394-3_25

Cited by

  1. The Applications of Hepatitis C Virus (HCV) Replication System in Developing Anti-HCV Reagents vol.45, pp.2, 2015, https://doi.org/10.4167/jbv.2015.45.2.171