Hepatitis C Virus (HCV) is a major Human pathogen. It persistently infects 170 million people worldwide. People infected with the virus might be asymptomatic at the beginning, however in c. 70 % of cases, they will develop a persistent infection, meaning that they will stay infected for the rest of their life, unless antiviral therapy is started. Persistently infected individuals are at high risk of developing serious liver diseases such as cirrhosis, steatosis, fibrosis and hepatocarcinoma. 

Untill very recently, only very few therapeutic options were available, mainly due to the fact that the virus poorly grows in cell culture. However, the situation has finally changed since the development of systems which allowed to study both viral RNA replication in cell culture (using the so-called "HCV Replicon system" (1)) and, more recently, the full viral life cycle (2, 3) thus creating the first "cell culture HCV" (HCVcc). 

These systems allowed to develop the first direct acting antivirals, approved for treatment of genotype 1 by the U.S. food and drug administration in 2011, and to begin understanding the life cycle of the virus and its pathogenic mechanisms more in detail (5, 6).

In the lab we use a wide range of techniques, including RNAi, biochemistry, live cell and immunofluorescence imaging in combination with HCVcc to dissect the molecular mechanisms regulating viral life cycle and identify new tatgets to fight HCV replication and pathogenesis.

 

REFERENCES

1.  Lohmann, V., Korner, F., Koch, J., Herian, U., Theilmann, L., and Bartenschlager, R. (1999) Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line, Science 285, 110-113.

2.     Wakita, T., Pietschmann, T., Kato, T., Date, T., Miyamoto, M., Zhao, Z., Murthy, K., Habermann, A., Krausslich, H. G., Mizokami, M., Bartenschlager, R., and Liang, T. J. (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome, Nat Med 11, 791-796.

3.     Zhong, J., Gastaminza, P., Cheng, G., Kapadia, S., Kato, T., Burton, D. R., Wieland, S. F., Uprichard, S. L., Wakita, T., and Chisari, F. V. (2005) Robust hepatitis C virus infection in vitro, Proc Natl Acad Sci U S A 102, 9294-9299.

4.      Lindenbach, B. D., Evans, M. J., Syder, A. J., Wolk, B., Tellinghuisen, T. L., Liu, C. C., Maruyama, T., Hynes, R. O., Burton, D. R., McKeating, J. A., and Rice, C. M. (2005) Complete replication of hepatitis C virus in cell culture, Science 309, 623-626.

5.      Li, Q., Brass, A. L., Ng, A., Hu, Z., Xavier, R. J., Liang, T. J., and Elledge, S. J. (2009) A genome-wide genetic screen for host factors required for hepatitis C virus propagation, Proc Natl Acad Sci U S A 106, 16410-16415.

6.      Tai, A. W., Benita, Y., Peng, L. F., Kim, S. S., Sakamoto, N., Xavier, R. J., and Chung, R. T. (2009) A functional genomic screen identifies cellular cofactors of hepatitis C virus replication, Cell host & microbe 5, 298-307.

 

READ MORE FROM OUR GROUP

 

1.         Alvisi, G., V. Madan, and R. Bartenschlager, Hepatitis c virus and host cell lipids An intimate connection. Rna Biology, 2011. 8(2): p. 258-269.

2.         Pichlmair, A., et al., Viral immune modulators perturb the human molecular network by common and unique strategies. Nature, 2012. 487(7408): p. 486-90.

3.         Ruggieri, A., et al., Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection. Cell Host Microbe, 2012. 12(1): p. 71-85.

4.         Amberkar, S., et al., High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay. World J Virol, 2013. 2(2): p. 18-31.

5.         Eberle, C.A., et al., The lysine methyltransferase SMYD3 interacts with hepatitis C virus NS5A and is a negative regulator of viral particle production. Virology, 2014. 462-463: p. 34-41.

6.         Metz, P., et al., Dengue Virus Inhibition of Autophagic Flux and Dependency of Viral Replication on Proteasomal Degradation of the Autophagy Receptor p62. J Virol, 2015. 89(15): p. 8026-41.

7.         Elbadawy, H.M., et al., Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line.Viruses, 2020. 12(9).