Robert M Krug

Summary

Affiliation: University of Texas
Country: USA

Publications

  1. ncbi request reprint Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein
    Robert M Krug
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA
    Virology 309:181-9. 2003
  2. ncbi request reprint The potential use of influenza virus as an agent for bioterrorism
    Robert M Krug
    Section of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA
    Antiviral Res 57:147-50. 2003
  3. pmc ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells
    Chen Zhao
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 107:2253-8. 2010
  4. pmc Interferon-induced ISG15 conjugation inhibits influenza A virus gene expression and replication in human cells
    Tien Ying Hsiang
    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
    J Virol 83:5971-7. 2009
  5. pmc Influenza A virus strains that circulate in humans differ in the ability of their NS1 proteins to block the activation of IRF3 and interferon-β transcription
    Rei Lin Kuo
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78746, USA
    Virology 408:146-58. 2010
  6. pmc Species specificity of the NS1 protein of influenza B virus: NS1 binds only human and non-human primate ubiquitin-like ISG15 proteins
    Haripriya Sridharan
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas, Austin, Texas 78712, USA
    J Biol Chem 285:7852-6. 2010
  7. pmc Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways
    Chen Zhao
    Institute for Cellular and Molecular Biology, University of Texas, 2500 Speedway, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 102:10200-5. 2005
  8. pmc The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target
    Karen Y Twu
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, 2500 Speedway, Austin, Texas 78712, USA
    J Virol 80:3957-65. 2006
  9. doi request reprint Identification of influenza virus inhibitors targeting NS1A utilizing fluorescence polarization-based high-throughput assay
    Eun Jeong Cho
    Texas Institute for Drug and Diagnostic Development, University of Texas at Austin, Austin, TX 78712, USA
    J Biomol Screen 17:448-59. 2012
  10. pmc Interaction of the influenza a virus nucleocapsid protein with the viral RNA polymerase potentiates unprimed viral RNA replication
    Laura L Newcomb
    Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA
    J Virol 83:29-36. 2009

Research Grants

Collaborators

Detail Information

Publications39

  1. ncbi request reprint Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein
    Robert M Krug
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA
    Virology 309:181-9. 2003
  2. ncbi request reprint The potential use of influenza virus as an agent for bioterrorism
    Robert M Krug
    Section of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA
    Antiviral Res 57:147-50. 2003
    ..Consequently, new antiviral drugs need to be developed, and the few currently available antiviral drugs should be stockpiled...
  3. pmc ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells
    Chen Zhao
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 107:2253-8. 2010
    ....
  4. pmc Interferon-induced ISG15 conjugation inhibits influenza A virus gene expression and replication in human cells
    Tien Ying Hsiang
    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
    J Virol 83:5971-7. 2009
    ..In contrast, we show that in mouse embryo fibroblasts ISG15 conjugation not only does not affect influenza A virus replication but also does not contribute to the IFN-induced antiviral activity against influenza A virus gene expression...
  5. pmc Influenza A virus strains that circulate in humans differ in the ability of their NS1 proteins to block the activation of IRF3 and interferon-β transcription
    Rei Lin Kuo
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78746, USA
    Virology 408:146-58. 2010
    ..Further, we show that TRIM25 binds the NS1 protein whether or not IRF3 activation is blocked, demonstrating that binding of TRIM25 by the NS1 protein does not necessarily lead to the blocking of IRF3 activation...
  6. pmc Species specificity of the NS1 protein of influenza B virus: NS1 binds only human and non-human primate ubiquitin-like ISG15 proteins
    Haripriya Sridharan
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas, Austin, Texas 78712, USA
    J Biol Chem 285:7852-6. 2010
    ..Consequently, the ISG15 proteins of humans and non-human primates are the only mammalian ISG15 proteins that would bind NS1B...
  7. pmc Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways
    Chen Zhao
    Institute for Cellular and Molecular Biology, University of Texas, 2500 Speedway, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 102:10200-5. 2005
    ..By targeting a wide array of constitutively expressed proteins, ISG15 conjugation greatly extends the repertoire of cellular functions that are affected by IFN-alpha/beta...
  8. pmc The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target
    Karen Y Twu
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, 2500 Speedway, Austin, Texas 78712, USA
    J Virol 80:3957-65. 2006
    ....
  9. doi request reprint Identification of influenza virus inhibitors targeting NS1A utilizing fluorescence polarization-based high-throughput assay
    Eun Jeong Cho
    Texas Institute for Drug and Diagnostic Development, University of Texas at Austin, Austin, TX 78712, USA
    J Biomol Screen 17:448-59. 2012
    ..Overall, the FP-based binding assay demonstrated its superior capability for simple, rapid, inexpensive, and robust identification of NS1A inhibitors and validation of their activity targeting NS1A...
  10. pmc Interaction of the influenza a virus nucleocapsid protein with the viral RNA polymerase potentiates unprimed viral RNA replication
    Laura L Newcomb
    Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA
    J Virol 83:29-36. 2009
    ....
  11. ncbi request reprint Virology. Clues to the virulence of H5N1 viruses in humans
    Robert M Krug
    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
    Science 311:1562-3. 2006
  12. ncbi request reprint A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis
    Ji Young Min
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, room 2 122, 2500 Speedway, University of Texas at Austin, Austin, TX 78712, USA
    Virology 363:236-43. 2007
    ..This interaction would occur in the nucleus, whereas PKR would bind to NS1A proteins in the cytoplasm prior to their import into the nucleus...
  13. pmc Sequence in the influenza A virus nucleoprotein required for viral polymerase binding and RNA synthesis
    Jesper K Marklund
    Department of Molecular Genetics and Microbiology, Institute for Cell and Molecular Biology, University of Texas at Austin, Texas, USA
    J Virol 86:7292-7. 2012
    ..In vitro binding experiments with purified virus polymerase and NPs established that these three amino acids are required for NP binding to the viral polymerase...
  14. pmc The H5N1 influenza virus NS genes selected after 1998 enhance virus replication in mammalian cells
    Karen Y Twu
    Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA
    J Virol 81:8112-21. 2007
    ..Consequently, these internal HK97 proteins largely compensate for the absence of F103 and M106, presumably by stabilizing the NS1A-CPSF30 complex...
  15. pmc Influenza a virus polymerase is an integral component of the CPSF30-NS1A protein complex in infected cells
    Rei Lin Kuo
    Institute for Cellular and Molecular Biology, University of Texas at Austin, 78712, USA
    J Virol 83:1611-6. 2009
    ....
  16. ncbi request reprint Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3' end processing of cellular pre-mRNAS
    Diana L Noah
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, 78712, USA
    Virology 307:386-95. 2003
    ..Mutation of this binding site in the NS1A protein also affects a second cellular antiviral response: in cells infected by the mutant virus, IFN-beta mRNA is produced earlier and in larger amounts...
  17. pmc Interferon-induced ISG15 pathway: an ongoing virus-host battle
    Chen Zhao
    Department of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
    Trends Microbiol 21:181-6. 2013
    ..Only the antiviral activity of human and non-human primate ISG15s can be blocked, providing one possible explanation for the restriction of influenza B virus to humans...
  18. pmc LGP2 downregulates interferon production during infection with seasonal human influenza A viruses that activate interferon regulatory factor 3
    Meghana Malur
    Department of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, USA
    J Virol 86:10733-8. 2012
    ..It is intriguing that LGP2, a host protein induced during influenza A virus infection, downregulates the host antiviral IFN response...
  19. pmc Synthesis and evaluation of quinoxaline derivatives as potential influenza NS1A protein inhibitors
    Lei You
    Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA
    Bioorg Med Chem Lett 21:3007-11. 2011
    ..The most active compounds (35 and 44) had IC(50) values in the range of low micromolar concentration without exhibiting significant dsRNA intercalation. Compound 44 was able to inhibit influenza A/Udorn/72 virus growth...
  20. pmc The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-alpha/beta-induced ubiquitin-like protein
    Chen Zhao
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 101:7578-82. 2004
    ....
  21. pmc 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
    Ji Young Min
    Section of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 103:7100-5. 2006
    ....
  22. ncbi request reprint Herc5, an interferon-induced HECT E3 enzyme, is required for conjugation of ISG15 in human cells
    Anahita Dastur
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, The University of Texas at Austin, 78712, USA
    J Biol Chem 281:4334-8. 2006
    ..These results demonstrate that Herc5 is required for conjugation of ISG15 to a broad spectrum of target proteins in human cells...
  23. pmc Roles of the phosphorylation of specific serines and threonines in the NS1 protein of human influenza A viruses
    Tien Ying Hsiang
    Department of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, USA
    J Virol 86:10370-6. 2012
    ..In contrast, phosphorylation of Ts or Ss in the NS1 protein of the 2009 H1N1 pandemic virus was not detected, indicating that NS1 phosphorylation probably does not play any role in the replication of this virus...
  24. ncbi request reprint Properties of the ISG15 E1 enzyme UbE1L
    Robert M Krug
    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
    Methods Enzymol 398:32-40. 2005
  25. pmc Emerging antiviral targets for influenza A virus
    Robert M Krug
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA
    Trends Pharmacol Sci 30:269-77. 2009
    ..Here, we describe how functional and structural studies led to the discovery of these novel targets and also how structural information is facilitating the rational design of new drugs against previously identified targets...
  26. pmc Reciprocal inhibition between intracellular antiviral signaling and the RNAi machinery in mammalian cells
    Gil Ju Seo
    The University of Texas at Austin, Molecular Genetics and Microbiology, 1 University Station A5000, Austin, TX 78712 0162, USA
    Cell Host Microbe 14:435-45. 2013
    ..Our results suggest that, unlike in lower eukaryotes, mammalian RISC is not antiviral in some contexts, but rather RISC has been co-opted to negatively regulate toxic host antiviral effectors via microRNAs. ..
  27. doi request reprint Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses
    Sanmitra Barman
    Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA
    Eur J Med Chem 71:81-90. 2014
    ..The phenyl containing compound had antiviral activity similar to that of the active form of oseltamivir (Tamiflu), and had no detectable effect on cell viability. ..
  28. ncbi request reprint Influenza virus virulence and its molecular determinants
    Diana L Noah
    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA
    Adv Virus Res 65:121-45. 2005
  29. ncbi request reprint Structural basis for ubiquitin-like ISG 15 protein binding to the NS1 protein of influenza B virus: a protein-protein interaction function that is not shared by the corresponding N-terminal domain of the NS1 protein of influenza A virus
    Weiming Yuan
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, 78712, USA
    Virology 304:291-301. 2002
    ..In particular, ISG15 and dsRNA can bind simultaneously; the binding of the ISG15 protein does not have a detectable effect on the binding of dsRNA, and vice versa...
  30. pmc Human influenza viruses activate an interferon-independent transcription of cellular antiviral genes: outcome with influenza A virus is unique
    Mee Jung Kim
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 99:10096-101. 2002
    ..This unique, global countermeasure against the early, IFN-alpha/beta-independent antiviral response of cells may be an important factor in the pathogenicity of influenza A virus infection...
  31. pmc Crucial role of CA cleavage sites in the cap-snatching mechanism for initiating viral mRNA synthesis
    Ping Rao
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA
    EMBO J 22:1188-98. 2003
    ..We present a new model for the influenza virus cap-snatching mechanism, which we postulate is a paradigm for the cap-snatching mechanisms of other segmented, negative-strand and ambisense RNA viruses...
  32. pmc Cellular DDX21 RNA Helicase Inhibits Influenza A Virus Replication but Is Counteracted by the Viral NS1 Protein
    Guifang Chen
    Department of Molecular Biosciences, Center of Infectious Disease, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
    Cell Host Microbe 15:484-93. 2014
    ....
  33. ncbi request reprint Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses
    Cuifeng Yin
    Center for Advanced Biotechnology and Medicine, Northeast Structural Genomics Consortium, Department of Molecular Biology and Biochemistry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA
    J Biol Chem 282:20584-92. 2007
    ..This pocket provides a target on the surface of the NS1 protein that is potentially suitable for the development of antiviral drugs targeting both influenza A and B viruses...
  34. ncbi request reprint Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA
    Shoudong Li
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Virology 349:13-21. 2006
    ..In addition, we demonstrated that PKR activation is inhibited in cells infected with a recombinant influenza A virus expressing NS1A mutant protein that cannot bind RNA, as is the case in cells infected with wild-type influenza A virus...
  35. ncbi request reprint 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
    Chen ya Chien
    Center for Advanced Biotechnology and Medicine and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854 5638, USA
    Biochemistry 43:1950-62. 2004
    ..This mode of dsRNA binding differs from that observed for any other dsRNA-binding protein...
  36. pmc Structural basis for suppression of a host antiviral response by influenza A virus
    Kalyan Das
    Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 105:13093-8. 2008
    ....
  37. ncbi request reprint The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA
    Qiaozhen Ye
    Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street, MS140, Houston, Texas 77005, USA
    Nature 444:1078-82. 2006
    ..Our results identify the tail loop binding pocket as a potential target for antiviral development...
  38. ncbi request reprint Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines
    Jukka Sirén
    Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
    Microbes Infect 8:2013-20. 2006
    ..In conclusion, our results show that in epithelial cells influenza A virus-induced antiviral cytokine gene expression is triggered by RIG-I and mda-5, whose expression is positively regulated by IFN-alpha...
  39. pmc Nuclear and nucleolar targeting of influenza A virus NS1 protein: striking differences between different virus subtypes
    Krister Melen
    Department of Viral Diseases and Immunology, National Public Health Institute, Mannerheimintie 166, FIN 00300, Helsinki, Finland
    J Virol 81:5995-6006. 2007
    ..It is likely that the evolutionarily well-conserved nucleolar targeting function of NS1A protein plays a role in the pathogenesis of influenza A virus...

Research Grants2

  1. Targeting the NS1 Protein for the Development of Influenza Virus Antivirals
    ROBERT KRUG; Fiscal Year: 2007
    ..In addition, the Paessler laboratory at the University of Texas Medical Branch will carry out animal experiments to test our inhibitory compounds. ..
  2. REPLICATION OF INFLUENZA VIRUS
    ROBERT KRUG; Fiscal Year: 2008
    ..Elucidation of the molecular mechanisms by which ISG15 conjugation inhibits influenza A and B viruses may lead to therapies that exploit these mechanisms. ..