Research Assistant Professor
Email: Office Phone: 318-675-4505
Laboratory Phone: 318-675-5759
Office Fax: 318-675-5764
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 two Alphaherpesviruses: Equine herpesvirus 1 (EHV-1) and varicella zoster virus (VZV)
The long-term goal in 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 IEP possesses several domains essential for trans-activation including an acidic trans-activation domain (TAD), nuclear localization signal (NLS), and binding domains for DNA and general transcription factors. However, the mechanism by which the IEP TAD functions in activating transcription remains unknown. We hypothesize that the IEP interacts with TBP, TFIIB, and TFIIA, and that its TAD stimulates gene expression by recruiting components of the RNA polymerase II machinery, such as Mediators and TBP-associated factors (TAFs), and that these interaction(s) generate a functional preinitiation complex on viral promoters. The EHV-1 IEP amino acid sequence has a high degree of homology to varicella zoster virus (VZV) immediate-early protein 62 (IE62). Thus, one aim is to compare the molecular mechanisms by which the EHV-1 IEP and VZV IE62 activate viral gene expression.
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 TAD and serine-rich tract essential for trans-activation and viral growth. Transient transfection assays showed that the regulatory IR2P 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. The IR2P interacted with TFIIB and TBP, and inhibited virus production. We hypothesize that the IR2P functions as a dominant-negative regulator of EHV-1 gene expression by blocking the formation of IEP preinitiation complex and/or by squelching the limited supplies of TFIIB and TBP. Thus, we seek to define the mechanism(s) by which the IR2P inhibits EHV-1 gene expression and replication.
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.
Ebner, P. D., S. K. Kim, and D. J. O'Callaghan. 2008. Biological and genotypic properties of defective interfering particles of equine herpesvirus 1 that mediate persistent infection. Virology 381:98-105.
Kim, S. K., S. Kim, G. Dai, Y. Zhang, B. C. Ahn, and D. J. O'Callaghan. 2011. Identification of functional residues of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication. Virology 417:430-442.
Kim, S., G. Dai, D. J. O’Callaghan, and S. K. Kim. 2012. Characterization of cis-acting elements required for autorepression of the equine herpesvirus 1 IE gene. Virus Research 165:52-60.
Dai, G., S. Kim, D. J. O’Callaghan, and S. K. Kim. 2012. Development of a bacterial artificial chromosome (BAC) recombineering procedure using galK-untranslated region (UTR) for the mutation of diploid genes. Journal of Virological Methods. doi:10.1016/j.jviromet.2012.02.010 (online publication).
All Publications: PubMed