Research Lab Members:
Hsiang, Tien-Ying (Tina)
Kuo, Rei-Lin
Leavitt, John
Liu, Chris
Malur, Meghana
Marklund, Jesper
Park, Jang Won
Smith, Bart
Sridharan, Haripriya
Zhao, Chen
Zhou, Ligang
Research Summary:
The major focus of the Krug laboratory is the molecular biology of human influenza viruses (influenza A and B viruses), which cause widespread human disease. We are determining the molecular mechanisms of viral mRNA synthesis and viral RNA replication; and how the viral nonstructural proteins of these two influenza viruses contribute to pathogenesis and overcome host defense by inhibiting crucial cellular functions, including the 3’ end processing system used for the production of cellular pre-mRNAs, and the interferon-induced modification of proteins by the ISG15 ubiquitin-like protein. Our research has already identified promising new targets for the development of antivirals, which are now the subject of high-throughput screens. In addition, research on influenza A viruses includes the analysis of the functions of the genes of H5N1 avian influenza viruses, which have the potential for causing the next pandemic.
Publications:
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2009
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Newcomb, L.L., Kuo, R.L., Ye, Q., Jiang, Y., Tao, Y.T., and Krug, R.M.,
Interaction of the influenza A virus nucleocapsid protein with the viral RNA polymerase potentiates unprimed viral RNA replication.,
J. Virol.
83:
29-36
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2008
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Kuo RL, Krug RM.,
Influenza a virus polymerase is an integral component of the CPSF30-NS1A protein complex in infected cells.,
J. Virol.
83:
1611-1616
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2008
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Das K, Ma LC, Xiao R, Radvansky B, Aramini J, Zhao L, Marklund J, Kuo RL, Twu KY, Arnold E, Krug RM, Montelione GT.,
Structural basis for suppression of a host antiviral response by influenza A virus.,
Proc. Natl. Acad. Sci. USA
105:
13093-13098
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2007
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Yin, C., Khan J.A., Swapna G.V., Ertekin A., Krug R.M., Tong L and Montelione G.T.,
Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from Influenza A and B viruses,
J. Biol. Chem.
282:
20584-20592
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2007
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Melen, K., Kinnunen, L., Fagerlund, R., Ikonen, N., Twu, K.Y., Krug, R.M. and Julkunen, I.,
Nuclear and nucleolar targeting of influenza A virus NS1A protein: Striking differences between different virus subtypes,
Journal of Virology
81:
5995-6006
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2007
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Min, .JY., Li, S., Sen, G.C. and Krug, R.M.,
A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis,
Virology
363:
236-243
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2007
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Twu, K.Y., Kuo, RL., Marklund, J., and Krug, R. M.,
The H5N1 influenza virus NS genes selected after 1998 enhance virus replication in mammalian cells,
J Virol
81:
8112-8121
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2006
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Ye, Q., Krug, R.M. and Tao, Y.J.,
The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA,
Nature
444:
1078-1082
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2006
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Min, J.-Y. and Krug, R. M.,
The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: Inhibiting the 2'-5' oligo (A) synthetase / RNase L pathway,
Proc. Natl. Acad. Sci. USA
103:
7100-7105
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2006
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Twu, K. Y., Noah, D. L., Rao, P., Kuo, R.-L., and Krug, R. M.,
The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target,
Journal of Virology
80:
3957-3965
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2005
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Zhao, C., Denison, C., Huibregtse, J. M., Gygi, S. and Krug, R.M.,
Human ISG15 targets both interferon-induced and constitutively expressed proteins functioning in diverse cellular pathways,
Proc. Natl. Acad. Sci. USA
102:
10200-10205
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2004
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Chien, C-Y, Xu, Y., Xiao, R., Aramini, J.M., Sahasrabudge, P.V., Krug, R.M., and Montelieone, G.T.,
Biophysical characterization of the complex between double-stranded RNA and the N-terminal domain of the NS1 protein from influenza A virus: evidence for a novel RNA-binding mode.,
Biochemistry
43:
1950-1962
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2004
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Zhao, C. Beaudenon, S.L., Kelley, M.L., Waddell, M.B., Yuan, W., Schulman, B.A., Huibregtse, J.M. and Krug, R.M.,
The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an interferon a/b-induced ubiquitin-like protein,
Proc. Natl. Acad. Sci. U.S.A.
101:
7578-7582
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2003
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Krug, R.M., Yuan, W., Noah, D.L. and Latham, A.G.,
Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein,
Virology
309:
181-189
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