Christoph Seeger, PhD
Office Phone: 215-728-4312
We are interested in the biology of human pathogenic viruses with an emphasis on mechanisms of viral replication and host-virus interactions that play a role in innate immunity. Our investigations on hepatitis B virus (HBV) lead to the identification of the signals required for reverse transcription of the viral DNA and provided the basis for the current model for hepadnavirus replication. We discovered that the hepatitis B polymerase could be expressed in enzymatically active form in the presence of the heat shock protein 90 complex. Moreover, we demonstrated that recovery from chronic hepatitis B infections requires massive destruction of infected hepatocytes. Investigations on hepatitis C virus (HCV) lead to the discovery that HCV replication could occur in cells of non-hepatic origin in human and mouse cells and hence did neither depend on hepatocyte –or primate-specific factors. We demonstrated that IFN resistance observed in patients was not caused by the emergence of IFN-resistant variants, but rather reflected resistance of hepatocytes to induce an effective antiviral program normally induced by IFN. Furthermore, we discovered that, in contrast to HCV, West Nile virus (WNV) could block the IFN response by inhibiting the phosphorylation of the Janus kinases Jak1 and Tyk2.
In line with our interest in HBV biology, the goal of our current research effort is to investigate one of the least understood steps in HBV replication: the mechanism by which the viral genome is converted into a covalently closed circular (CCC) DNA form and how intracellular amplification of CCC DNA is regulated. In addition, we are exploring a novel strategy to eliminate CCC DNA from infected cells with the help of sequence specific effector nucleases.Description of research projects
- Seeger C, Sohn JA. Targeting HBV cccDNA with CRISPR/Cas9. (submitted).
- Chisari FV, Mason WS, Seeger C. Virology. Comment on “Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA”. Science. 2014;344:1237. PubMed
- Seeger C, Zoulim F, Mason WS. Hepadnaviruses. In: Fields Virology 6th edition (Howley P, Knipe D, Eds.). 2013. Lippincott, Williams & Wilkins, NY, pp. 2185-2221
- Seeger C, Mason WS. Sodium-dependent taurocholic cotransporting polypeptide: a candidate receptor for human hepatitis B virus. Gut. 2013;62:1083-1095. PubMed
- Evans JD, Crown RA, Sohn JA, Seeger C. West Nile Virus infection induces depletion of IFNAR1 protein levels. Viral Immunol. 2011;24:253-263. PubMed
- Sohn JA, Litwin S, Seeger C. Mechanism for CCC DNA synthesis in hepadnaviruses. PLoS ONE. 2009;4:e8093. PubMed
- Stiffler JD, Nguyen M, Sohn JA, Liu C, Kaplan D, Seeger C. Focal distribution of hepatitis C virus RNA in infected livers. PLoS ONE. 2009;4:e6661. PubMed
- Evans JD, Seeger C. Differential effects of mutations in NS4B on West Nile virus replication and inhibition of interferon signaling. J Virol. 2007;81:11809-16. PubMed
- Guo JT, Hayashi J, Seeger C. West Nile virus inhibits the signal transduction pathway of alpha interferon. J Virol. 2005;79:1343-1350. PubMed
- Hayashi J, Stoyanova R, Seeger C. The transcriptome of HCV replicon expressing cell lines in the presence of alpha interferon. Virology. 2005;335:264-75. PubMed
- Guo JT, Zhu Q, Seeger C. Cytopathic and noncytopathic interferon responses in cells expressing hepatitis C virus subgenomic replicons. J Virol. 2003;77:10769-79. PubMed
- Zhu Q, Guo JT, Seeger C. Replication of hepatitis C virus subgenomes in nonhepatic epithelial and mouse hepatoma cells. J Virol. 2003;77:9204-10. PubMed