Faculty

Krug, Robert
Chair, Molecular Genetics and Microbiology,
Lorene Morrow Kelley Fellow In Microbiology

E-mail

Website

Main Office: MBB 2.122BA
Phone: (512) 232-5563

Alternate Office: MBB 2.122
Phone: (512) 232-5566

Mailing Address:
The University of Texas at Austin
Section of Molecular Genetics and Microbiology
2500 Speedway Stop A4800
Austin, TX 78712-1191

Graduate Student

• Liu, Chris - Graduate Student
• Malur, Meghana - Graduate Student
• Marklund, Jesper - Graduate Student
• Smith, Bart - Graduate Student

Post Doctoral

• Collins, Mark - Post Doctoral
• Hsiang, Tien-Ying (Tina) - Post Doctoral
• Zhou, Ligang - Post Doctoral

Staff

• Chen, Ran - Staff
• Zhao, Chen - Staff



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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-prime 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.


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Publications:

2010	Sridharan, H., Zhao, C., and Krug, R. M., Species specificity of the NS1 protein of influenza B virus: NS1 binds only human and non-human primate ubiquitin-like proteins, J. Biol. Chem. 285:7852-7856.
2010	Zhao, C., Hsiang, T.-Y., Kuo, R.-L. and Krug, R. M., ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells, Proc. Natl. Acad. Sci. USA 107:2253-2258.
2009	Das, K., Aramini, J. M., Ma, L.-C., Krug, R. M. and Arnold, E. , Structures of influenza A proteins and insights into antiviral drug targets, Nat. Struct. Mol. Biol. 17:530-538.
2009	Krug, R.M. and Aramini, J.M. , Emerging antiviral targets for influenza A virus, Trends Pharmacol Sci. 30:269-277.
2009	Hsiang, T.-Y., Zhao, C. and Krug, R. M. , Interferon-induced ISG15 conjugation inhibits influenza A virus gene expression and replication in human cells, J. Virol 83:5971-5979.
2009	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.
2009	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.
2008	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.
2007	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.
2007	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.
2007	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.
2007	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.
2006	Siren, J., Imaizumi, T., Sarkar, D., Pietila, T., Noah, D. L., Hiscott, J., Krug, R. M., Fisher, P. B., Julkunen, I., and Matikainen, S., Retinoic acid inducible gene-1 and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines, Microbes Infect 8:2013-2020.
2006	Krug, R.M., Clues to the virulence of H5N1 viruses in humans, Science 311:1562-1563.
2006	, S., Min, J.-Y., Krug, R. M. and Sen, G. C. , Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA, Virology 349:13-21.
2006	Dastur, A., Beaudenon, S., Kelley, M., Krug, R. M. and Huibregtse, J. M., Herc5, an interferon-induced HECT E3 enzyme, is required for conjugation of ISG15 in human cells, J. Biol. Chem. 281:4334-4338.
2006	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.
2006	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.
2006	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.
2005	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.
2005	Noah, D. L. and Krug, R. M., Influenza virus virulence and its molecular determinants, Advances in Virus Research 65:121-146.
2005	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.
2004	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.
2004	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.
2003	Rao, P., Yuan, W. and Krug, R. M., The crucial role of CA endonuclease cleavage sites in the cap-snatching mechanism for the initiation of viral messenger RNA synthesis, EMBO J 22:1188-1198.
2003	Noah, D. L., Twu, K. Y. and Krug, R. M., Cellular antiviral responses against influenza A virus are countered at the post-transcriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3’ end processing of cellular pre-mRNAs, Virology 307:386-395.
2003	Krug, R. M. , potential use of influenza virus as an agent for bioterrorism, Antiviral Research 57:147-150.
2003	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.