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Instructor
Contact Information:
Email: skim1@lsuhsc.edu
Office Phone: 318-675-4505
Laboratory Phone: 318-675-5759
Office Fax: 318-675-5764
Education/Training:
Postdoctoral Study, Seoul National University and Louisiana State University Health Sciences Center - Shreveport
Ph.D., Molecular Biology, 1992, Seoul National University
M.S., Molecular Biology/Zoology, 1988, Seoul National University
B.S., Molecular Biology/Zoology, 1985, Seoul National University
Major Research Interests:
Gene expression and regulation of the Equine Herpesvirus 1 (EHV-1).
The long-term goal our laboratory is to determine how the key EHV-1 regulatory proteins govern viral gene expression. EHV-1 is an important pathogen of equines and a useful model to investigate Alphaherpesvirus gene regulation as its gene program is initiated by expression of a single immediate-early (IE) gene that encodes the IE protein (IEP) of 1,487 amino acids, which activates expression of >50 early (E) genes. The IR2 gene is an early regulatory gene that maps within the open reading frame of the IE gene and encodes the IR2 protein (IR2P). The IR2P is a truncated form (1,165 amino acids) of the IEP and lacks residues 1 to 322 that harbor the trans-activation domain (TAD) and serine-rich tract (SRT) essential for trans-activation and viral growth. Transient transfection assays showed that the early regulatory IR2P by itself down-regulated the IE promoter and all early promoters tested and abrogated activation of viral promoters mediated by the IEP and the early regulatory protein UL5P in a dose-dependent manner. The IR2P interacted with the general transcription factors TFIIB and TBP. Virus growth assays revealed that the IR2P inhibited virus production by up to 90-fold in equine NBL6 cells. On the basis of these findings, we hypothesize that the IR2P functions as a dominant-negative regulator of EHV-1 gene expression by blocking IEP-binding to viral promoter sequences and/or squelching the limited supplies of TFIIB and TBP. Thus, our overall goals are to characterize the biological and molecular properties of the IR2P and to define the mechanism(s) by which the IR2P inhibits EHV-1 gene expression and replication.
Representative Publications:
Kim, S. K., H. K. Jang, R. A. Albrecht, W. A. Derbigny, Y. Zhang, and D. J. O'Callaghan. 2003. Interaction of the equine herpesvirus 1 ICP0 protein with the immediate-early (IE) protein, TFIIB, and TBP may mediate the antagonism between the IE and EICP0 proteins. Journal of Virology 77:2675-2685.
Albrecht, R. A., H. K. Jang, S. K. Kim, and D. J. O'Callaghan. 2003. Direct interaction of TFIIB the IE protein of equine herpesvirus 1 is required for maximal trans-activation function. Virology 316:302-312.
Albrecht R. A., S. K. Kim, Y. Zhang, Y. Zhao, and D. J. O'Callaghan. 2004. The equine herpesvirus 1 EICP27 protein enhances gene expression via an interaction with TATA-binding protein. Virology 324:311-326.
Kim, S. K., R. A. Albrecht, and D. J. O'Callaghan. 2004. A negative regulatory element (base pairs -204 to -177) of the EICP0 promoter of equine herpesvirus 1 abolishes the EICP0 protein's trans-activation of its own promoter. Journal of Virology 78:11696-11706.
Albrecht R. A., S. K. Kim, and D. J. O'Callaghan. 2005. The EICP27 protein of equine herpesvirus 1 is recruited to viral promoters by its interaction with the immediate-early protein. Virology 333:74-87.
Buczynski K. A., S. K. Kim, and D. J. O'Callaghan. 2005. Initial characterization of 17 viruses harboring mutant forms of the immediate-early equine herpesvirus 1. Virus Gene 31:229-239.
Kim S.K., B. C. Ahn, R. A. Albrecht, and D. J. O'Callaghan. 2006. The unique IR2 protein of equine herpesvirus 1 (EHV-1) negatively regulates EHV-1 gene expression. Journal of Virology 80:5041-5049.
Ahn B. C., J. E. Breitenbach, S. K. Kim, and D. J. O'Callaghan. 2007. The equine herpesvirus-1 IR3 gene that lies antisense to the sole immediate-early (IE) gene is trans-activated by the IE protein, and is poorly expressed to a protein. Virology 363:15-25.
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