Research Associate 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
Our long-term goal is to determine how the key EHV-1 regulatory proteins govern viral gene expression and replication. 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). 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 by inducing the expression of IFN-γ gene and 16 antiviral interferon-stimulated genes (ISG). These results suggest that EHV-1 KyA may be used as a live attenuated EHV-1 vaccine in horses. The administration of IFN-γ inhibited EHV-1 replication and protected mice from lethal challenge, suggesting that IFN-γ serves as a novel prophylactic agent and may offer new strategies for the development of anti-EHV-1 agents in the equine. Our goal is to identify inhibition mechanism of EHV-1 infection by the innate immune response.
VZV is a ubiquitous human pathogen and establishes latency in sensory ganglia; upon reactivation, the virus migrates to the skin via axonal transport to cause zoster (shingles). IFN-γ is a potent cytokine produced following primary VZV infection. How VZV overcomes this cutaneous IFN-γ barrier and produces skin vesicles is not known. Our results showed that pretreatment with IFN-γ effectively inhibited VZV replication and immediate-early 62 protein (IE62)-mediated trans-activation in lung epithelial A549 and retinal epithelial ARPE-19 cells but not in skin melanoma MeWo cells. IE62, a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. These results led us to hypothesize that IFN-γ blocks VZV replication by inhibiting IE62 function in a cell line-dependent manner. Functional mechanisms of IFN-γ in VZV replication could provide important biological roles of IFN-γ in viral gene programming, but also identify factors contributing to the tissue restriction of VZV.
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.
Kim, S. K., A. K. Shakya, and D. J. O’Callaghan. 2016. Immunization with attenuated equine herpesvirus 1 strain KyA induces innate immune responses that protect mice from lethal challenge. Journal of Virology 90: 8090-8104. PMID: 27356904
Shakya, A. K., D. J. O’Callaghan, and S. K. Kim. 2017. Comparative genomic sequencing and pathogenic properties of equine herpesvirus 1 KyA and RacL11. Front. Vet. Sci. 4:211. PMID: 29312962
All Publications: PubMed