Research Assistant Professor
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
Gene expression and regulation of equine herpesvirus 1 (EHV-1) and varicella-zoster virus (VZV)
Our long-term goal is to determine how the key EHV-1 and VZV 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) which activates expression of >50 early (E) genes. The IEP possesses several domains essential for trans-activation including an acidic trans-activation domain (TAD) 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. VZV is a ubiquitous human pathogen that causes chickenpox in primary lytic infection and shingles during reactivation from latent infection. The EHV-1 IEP amino acid sequence has a high degree of homology to 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 EHV-1 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 lacks the TAD and serine-rich tract essential for trans-activation and viral growth. The regulatory IR2P down-regulates all early promoters tested, and inhibits virus production. We seek to define the mechanism(s) by which the IR2P inhibits EHV-1 gene expression and replication.
We are also interested in understanding the protective mechanisms of EHV-1 attenuated KyA in CBA mice. EHV-1 KyA immunization effectively protected CBA mice from pathogenic RacL11 challenge infection by inducing the expression of IFN-γ gene and 16 antiviral interferon-stimulated genes (ISG). Our findings may offer new strategies for the development of anti-EHV-1 agents in the equine.
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).
Zhang, Y., R. A. Charvat, S. K. Kim, and D. J. O’Callaghan. 2014. The EHV-1 UL4 protein that tempers viral gene expression interacts with cellular transcription factors. Virology 449:25-34.
Kim, S. K., A. K. Shakya, and D. J. O’Callaghan. 2016. Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence. Virus Research. 211: 222 – 232.
Kim, S. K., A. K. Shakya, S. Kim, and D. J. O’Callaghan. 2016. Functional characterization of the serine-rich tract of varicella-zoster virus IE62. Journal of Virology. In press.
All Publications: PubMed