Department of Biochemistry
Yonsei University
PhD: University of Wisconsin-Madison
Post-doc : Fox Chase Cancer Center
Molecular Understanding of Hepadnavirus Infection
Chronic hepatitis remains the major fatal liver diseases in many area of the globe. In particular, over 5 % of world population is chronically infected with hepatitis B virus (HBV) and these individual has a high risk of liver diseases such as hepatitis, liver cirrhosis, and liver cancer. The work in my laboratory is focused on understanding molecular aspects of hepadnaviruses infection. We are mainly using human hepatitis B virus (HBV) as a model, a prototype of hepadnavirus family. Although it has a DNA genome, it replicates via reverse transcription of an RNA template, pregenomic RNA (pgRNA). In particular, we are interested in molecular aspect of viral reverse transcription.
The major approach has been to create mutations in a cloned DNA copy of the viral genome by site-directed mutagenesis and to determine the effect of the mutations on the viral life cycle after transfer of the altered DNAs into hepatoma cells in culture. These genetic analyses have defined the functional domains of various viral proteins and the sites of their action on viral nucleic acids. Recently, we reported a novel strand-transfer mechanism occurring during minus-strand DNA synthesis of viral reverse transcription [(Virology 371:32-373(2008)]. In addition, we reported that HBV polymerase suppresses translation of pgRNA, implicating a regulatory role of HBV polymerase in rergulating switching from translation to genome replication [Virology 373:112-123 (2008)]. In future, we aim to define host factors that contribute to viral reverse transcription via interaction with HBV polymerase or recognition of specific sequence elements on the pgRNA.
We are also interested in defining actual role of HBx, a small viral regulatory protein in its ability in supporting the viral genome replication. We established oncogenic potency of HBx in the context of liver cancer (Oncogene 20: 16, 2001; Hepatology 39:1683, 2004). Establishment of a robust replicon system by using hepatoma cells in culture, that critically depends on the HBx, enables us to address how HBx stimulates the viral reverse transcription. (2008/12/24)
Lim, W.Kwon, S-H, Cho, H., Kim, S., Lee, S, Ryu, W.-S., Cho, H. HBx targeting to mitochondria and ROS generation are necessary but insufficient for HBV-induced cyclooxygenase-2 expression. J. Mol. Med. (in press)
Kim, S., H. Wang, W.-S. Ryu. Incorporation of eukaryotic translation factor eIF4E into viral nucleocapsids via interaction with hepatitis B viral polymerase. J. Virol. (accepted)
Kim, S, J. Lee, and W.-S. Ryu. Four Conserved Cysteine Residues of the Hepatitis B Virus Polymerase are Critical for RNA Pregenome Encapsidation. J. Virol. 83:8032-8040(2009)
Lee, J., W.-S. Ryu. Insertion or deletion mutagenesis by overlap extension PCR. In: Braman, J, ed. In Vitro
Mutagenesis Protocols. Totowa, NJ: Humana Press (In press).
Wang, H.F., S. Kim, W.-S. Ryu. DDX3 DEAD-box RNA helicase inhibits hepatitis B viral reverse transcription by incorporation into nucleocapsids. J. Virol. 83:5815-5824(2009)
Hussain, Z. H.-S. Jung, D.-K., Ryu, and W.-S. Ryu. Genetic dissection of naturally occurring basal core promoter mutations of hepatitis B virus reveals the silent phenotype in the overlapping X gene. J. Gen. Virol. 90:2272-2281(2009)
Cha, M.-Y, D.-K. Ryu, H.-S. Jung, H.-E, Chang, W.-S. Ryu. Stimulation of Hepatitis B Virus Genome Replication by HBx is Linked to Both Nuclear and Cytoplasmic HBx Expression. J. Gen. Virol. 90:978-986(2009)
Lee, H.-J. J. Lee , M. K. Shin and W.-S. Ryu. Polyadenylation is dispensable for hepadnaviral reverse transcription. Mol. Cells. 25: 545-552 (2008)
Ryu, D.-K., S. Kim, and W.-S. Ryu. Hepatitis B virus polymerase suppresses translation of pregenomic RNA via a mechanism involving its interaction with 5' stem-loop structure. Virology 373:112-123 (2008)
Shin, M.-K., J.-H. Kim, D.-K. Ryu, and W.-S. Ryu. Circularization of an RNA template via long-range base pairing is critical for hepadnaviral reverse transcription. Virology 371:362-373 (2008)
Sohn, S.-Y., J.-H. Kim, K.-W. Baek, W.-S. Ryu, and B.-Y. Ahn. Turnover of hepatitis B virus X protein is facilitated by Hdji, a human Hsp40/DnaJ protein. BBRC 347: 764-768 (2006)
Cha, M.-Y., C.-M. kim, Y.-M. Park, and W.-S. Ryu. Hepatitis B virus X protein is essential for the activation of Wnt/β-catenin signaling in hepatoma cell. Hepatology 39:1683-1693 (2004)
Shin, M.-K. J. Lee, and W.-S. Ryu. A Novel cis-acting Element Facilitates Minus-Strand DNA Synthesis During Reverse Transcription of the Hepatitis B Viruses Genome. J. Virol. 78:6252-6262 (2004)
Lee, J., M.-K Shin, H.-J. Lee, and W.-S. Ryu. Identification of three novel cis-acting elements required for efficient plus-strand DNA synthesis of hepatitis B virus genome. J. Virol. 78:7455-7464 (2004)
Lee, J., H.-J. Lee, M.-K Shin. and W.-S. Ryu. Versatile PCR-mediated insertion or deletion mutagenesis. BioTechniques 36:398-400 (2004)