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Susan
C. Baker, Ph.D.
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The focus of my research is to study mechanisms of viral replication. If we can understand how viruses replicate their genetic information, we can design approaches to block virus replication and pathogenicity. I study the replication process of murine coronavirus. Coronaviruses are a group enveloped RNA viruses which infect diverse species of animals causing respiratory, gastrointestinal and neurological disease. Mouse hepatitis virus, the prototype coronavirus, serves as a model system for the study of virus induced demyelination. I use molecular techniques to investigate the expression, proteolytic processing and function of the coronavirus RNA polymerase polyprotein. This complex polyprotein holds the key to understanding how coronavirus replication is regulated. In our investigation of the coronavirus replicase polyprotein, we found that the polyprotein is processed into at least 15 products by three distinct viral proteases. Although proteolytic processing of a precursor polyprotein is a common strategy used by RNA viruses, the processing of the coronavirus replicase polyprotein is the most complex of the the viral replicases analyzed to date. Our current efforts are aimed at determining the functions of the replicase precursors and processed products and determining if proteolytic processing causes a switch in the RNA polymerase activity from synthesis of negative strand RNA to synthesis of positive strand RNA. The results of studies will provide us with new information on replicase that mediates RNA synthesis and RNA recombination, events which contribute to the ability of viruses to rapidly evolve and evade the immune system and hamper vaccine development. Selected PublicationsGrum-Tokars, V., Ratia, K., Begaye, A., Baker, S.C., Mesecar AD. 2007. Evaluating the 3C-like protease activity of SARS-Coronavirus: Recommendations for standardized assays for drug discovery. Virus Res. Mar 28; [Epub ahead of print] Chen, Z., Wang, Y., Ratia, K., Mesecar, A.D., Wilkinson, K. D., Baker, S.C. 2007. Proteolytic processing and deubiquitinating activity of papain-like proteases of human coronavirus NL63. J. Virol. 81: 6007-18. Kanjanahaluethai, A., Chen, Z., Jukneliene, D., Baker, S. C. 2007. Membrane topology of murine coronavirus replicase nonstructural protein 3. Virology 361:391-401. Snyder, E.E., Kampanya, N, ,et al. PATRIC: the VBI PathoSystems Resource Integration Center. Nucleic Acids Res. 2007 Jan;35(Database issue):D401-6.
Ratia, K., K.S. Saikatendu, B.D. Santarsiero, N. Barretto, S.C. Baker, R.C. Stevens, and A.D.
Mesecar (2006). SARS coronavirus papain-like protease: structure of a viral deubiquitinating enzyme.
Proc. Natl. Acad. Sci. 103: 5717-5722. Gosert, R., A. Kanjanahaluethai, D. Egger, K. Bienz, and S. C. Baker (2002). RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J. Virol. 76: 3698-3708. Kanjanahaluethai, A. and S. C. Baker (2000). "Identification of mouse hepatitis virus papain-like proteinase 2 activity. J Virol 74: 7911-7921. Search PubMed for a complete listing of Susan Baker's publications.
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