B.A. Alfred University (1968)
M.D., Ph.D. Albert Einstein College of Medicine (1975)
The replication of the murine coronavirus MHV (mouse hepatitis virus) and the molecular and genetic basis of its interactions with the host are being studied. Coronaviruses are important human pathogens causing a broad range of diseases depending on the particular virus and host system examined. Human diseases associated with coronaviruses include SARS (severe acute respiratory syndrome), less severe lower and upper respiratory disease, and gastroenteritis. MHV produces a broad spectrum of disease in the mouse, and provides excellent small animal models for hepatitis, for SARS, and for multiple sclerosis.
We have two projects in the laboratory. In collaboration with investigators in Toronto and Pennsylvania my laboratory has developed a MHV model for SARS. We are currently developing genetic tools to allow us to determine the role of various coronavirus proteins in the pathogenesis of SARS. The second project is focused on understanding how cis-acting sequences at the 5' and 3' untranslated regions (UTRs) function in replication. We have developed a novel model of structure of the 5'UTR and we are examining the role of the individual RNA stem-loop structures predicted by this model in viral replication. Studies in my laboratory have identified a structurally dynamic region of the 5’UTR that interacts with the 3’UTR to facilitate transcription. We are investigating these interactions and their functional role in viral replication using biochemical, cell biologic, and reverse genetic approaches.
Li, L, Kang, H, Liu, P, Makkinje, N, Williamson, ST, Leibowitz, JL, Giedroc, DP: Structural lability in stem-loop 1 drives a 5' UTR-3' UTR interaction in coronavirus replication. J. Mol. Biol. 377:790-803, 2008. Link to PDF
Kang, H, Bardwarj, K, Li, Y, Palaninathan, S, Sacchettini, J, Linda Guarino, L, Leibowitz, JL, and Kao, CC: Biochemical and genetic analyses of the mouse hepatitis virus Nsp15 endoribonuclease. J Virol. 81:13587-13597, 2007. Link to PDF
Liu, P, Millership, JJ, Li, L, Giedroc, DP, and Leibowitz, JL: A U-turn motif-containing stem-loop in the coronavirus 5' untranslated region plays a functional role in replication. RNA 13:763-780, 2007. Link to PDF
Kang H, Feng M, Schroeder ME, Giedroc DP, Leibowitz JL.:Putative cis-acting stem-loops in the 5' untranslated region of the severe acute respiratory syndrome coronavirus can substitute for their mouse hepatitis virus counterparts. J. Virol. 80:10600-10614, 2006.
De Albuquerque N, Baig E, Ma X, Zhang J, He W, Rowe A, Habal M, Liu M, Shalev I, Downey GP, Gorczynski R, Butany J, Leibowitz J, Weiss SR, McGilvray ID, Phillips MJ, Fish EN, Levy GA: Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice. J Virol. 80:10382-10394, 2006.
Youn, S, Leibowtiz, JL, and Collisson, EW: In vitro assembled, recombinant infectious bronchitis viruses demonstrate that the 5a open reading frame is not essential for replication. Virology 332:206-215, 2005. Link to PDF
Johnson, RF, Feng, M, Liu, P, Millership, JJ, Yount, B, Baric, RS, Leibowitz, JL: The effect of mutations in the mouse hepatitis virus 3'(+)42 protein binding element on RNA replication. J. Virol. 79:14570-14585, 2005.
Nanda, SK, Johnson, RF, Liu, Q, and Leibowitz, JL: Mitochondrial HSP70, HSP40, and HSP60 bind to the 3' untranslated region of the mouse hepatitis virus genome. Arch. Virol. 149: 93-111, 2004.
Liu, M, Leibowitz, JL, Clark, DA, Medicine, M, Ning, Q, Ding, JW, D'Abreo, C, Fung, L, Marsden, PA, and Levy, GA: Gene transcription of fgl2 in endothelial cells is controlled by Ets-1 and Oct-1 and requires the presence of both Sp1 and Sp3. Eur. J. Biochem. 270:1-13, 2003.
Liu, Q, Johnson, RF, and Leibowitz, JL: Secondary structural elements within the 3' untranslated region of mouse hepatitis virus strain JHM genomic RNA. J. Virol. 75:12105-12113, 2001.
Nanda, S.K., and Leibowitz, J.L.: Mitochondrial aconitase binds to the 3'-untranslated region of the mouse hepatitis virus genome. J. Virol. 75:3352-3362, 2001.
Levy, GA, Liu, MF, Ding, JW, Yuwaraj, S, Leibowitz, JL, Marsden, PA, Ning, Q, Kovalinka, A, and Phillips, MJ: A molecular basis for fulminant viral hepatitis. Amer. J. Pathol. 156:1217-1225, 2000.