Research Topics
| ECKARD A WIMMERSummaryAffiliation: State University of New York Country: USA Publications
Research Grants
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Publications
The test-tube synthesis of a chemical called poliovirus. The simple synthesis of a virus has far-reaching societal implicationsEckard Wimmer
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY, USA
EMBO Rep 7:S3-9. 2006- Virus attenuation by genome-scale changes in codon pair biasJ Robert Coleman
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA
Science 320:1784-7. 2008..Polioviruses thus customized were used to immunize mice and provided protective immunity after challenge. This "death by a thousand cuts" strategy could be generally applicable to attenuating many kinds of viruses... 
Synthetic poliovirus and other designer viruses: what have we learned from them?Eckard Wimmer
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11790, USA
Annu Rev Microbiol 65:583-609. 2011..It also allows modification of viral genomes to an extent hitherto unthinkable. Recoding of poliovirus and influenza virus to develop new vaccine candidates and refactoring the phage T7 DNA genome are discussed as examples...- Synthetic viruses: a new opportunity to understand and prevent viral diseaseEckard Wimmer
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA
Nat Biotechnol 27:1163-72. 2009..Although only a few applications of virus synthesis have been described as yet, key recent findings have been the resurrection of the 1918 influenza virus and the generation of codon- and codon pair-deoptimized polioviruses... 
Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural templateJeronimo Cello
Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA
Science 297:1016-8. 2002..Our results show that it is possible to synthesize an infectious agent by in vitro chemical-biochemical means solely by following instructions from a written sequence...- Functional dissection of a poliovirus cis-acting replication element [PV-cre(2C)]: analysis of single- and dual-cre viral genomes and proteins that bind specifically to PV-cre RNAJiang Yin
Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, 11794, USA
J Virol 77:5152-66. 2003..We have further demonstrated that the viral proteins 3CD(pro) and 3C(pro) form stable complexes with a transcript PV-cre(2C) RNA that can be considered critical for VPg uridylylation... - Analysis of the cloverleaf element in a human rhinovirus type 14/poliovirus chimera: correlation of subdomain D structure, ternary protein complex formation and virus replicationElizabeth Rieder
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794-5222, USA
J Gen Virol 84:2203-16. 2003..Biochemical assays demonstrated that the function of the CL element and the function of the cis-acting replication element in the 3D(pol)-3CD(pro)-dependent uridylylation of VPg are not linked... - Replication of poliovirus requires binding of the poly(rC) binding protein to the cloverleaf as well as to the adjacent C-rich spacer sequence between the cloverleaf and the internal ribosomal entry siteHidemi Toyoda
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11790, USA
J Virol 81:10017-28. 2007..These data reveal a new essential function of the spacer between the CL and the IRES in poliovirus proliferation... - Live attenuated influenza virus vaccines by computer-aided rational designSteffen Mueller
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA
Nat Biotechnol 28:723-6. 2010..The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is especially relevant when dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza... - Growth phenotypes and biosafety profiles in poliovirus-receptor transgenic mice of recombinant oncolytic polio/human rhinovirusesJeronimo Cello
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794 5222, USA
J Med Virol 80:352-9. 2008..These findings highlight the safety of intracerebral inoculation of PVS(RIPO) for the treatment of human glioma... - Putting synthesis into biology: a viral view of genetic engineering through de novo gene and genome synthesisSteffen Mueller
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794 5222, USA
Chem Biol 16:337-47. 2009..For this reason viruses are once again poised to lead the way in the budding field of synthetic biology--for better or worse... - Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses and implications for global poliovirus eradicationPing Jiang
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794 5222, USA
Proc Natl Acad Sci U S A 104:9457-62. 2007..In a PV-free world without PV neutralizing antibodies, contemporary C-CAV, like their ancestor(s), could be fertile ground for a PV-like agent to emerge by mutation... - Oncolytic treatment and cure of neuroblastoma by a novel attenuated poliovirus in a novel poliovirus-susceptible animal modelHidemi Toyoda
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York 11794 5222, USA
Cancer Res 67:2857-64. 2007..We suggest that our novel attenuated oncolytic poliovirus is a promising candidate for effective oncolytic treatment of human neuroblastoma or other cancer even in the presence of present or induced antipolio immunity... - Reduction of the rate of poliovirus protein synthesis through large-scale codon deoptimization causes attenuation of viral virulence by lowering specific infectivitySteffen Mueller
Department of Molecular Genetics and Microbiology, Life Sciences Building, Stony Brook University, Stony Brook, NY 11794 5222, USA
J Virol 80:9687-96. 2006.... - Interaction of the poliovirus receptor CD155 with the dynein light chain Tctex-1 and its implication for poliovirus pathogenesisSteffen Mueller
Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11794, USA
J Biol Chem 277:7897-904. 2002..Association with Tctex-1 and, hence, with the dynein motor complex may offer an explanation for how poliovirus hijacks the cellular transport machinery to retrogradely ascend along the axon to the neuronal cell body... - cis-acting RNA signals in the NS5B C-terminal coding sequence of the hepatitis C virus genomeHaekyung Lee
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA
J Virol 78:10865-77. 2004..The other two stem-loops (SL-IV and SL-VII) of the NS5BCR domain were found to be important but not essential for colony formation by the subgenomic replicon. The precise function(s) of these cis-acting RNA elements is not known... - Mutation of a single conserved nucleotide between the cloverleaf and internal ribosome entry site attenuates poliovirus neurovirulenceNidia De Jesus
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Life Sciences Bldg, Stony Brook, NY 11794-5222, USA
J Virol 79:14235-43. 2005.... - Immunofluorescence analysis of poliovirus receptor expression in Peyer's patches of humans, primates, and CD155 transgenic mice: implications for poliovirus infectionAkiko Iwasaki
Department of Epidemiology and Public Health, School of Medicine, Yale University, New Haven, Connecticut, USA
J Infect Dis 186:585-92. 2002..This suggests that productive poliovirus infection of the gut is dependent on the expression of CD155 within the FAE, including the M cells, and on cells within Peyer's patches, most likely within germinal centers... - A "slide-back" mechanism for the initiation of protein-primed RNA synthesis by the RNA polymerase of poliovirusAniko V Paul
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York 11790, USA
J Biol Chem 278:43951-60. 2003..Furthermore, we observed that the spacing between G-1 and A-5 and the size of the loop affect the yield but not the nature of the VPg-linked products... - Stimulation of poliovirus RNA synthesis and virus maturation in a HeLa cell-free in vitro translation-RNA replication system by viral protein 3CDproDavid Franco
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11790, USA
Virol J 2:86. 2005..Our results indicate that the stimulation of RNA synthesis and virus maturation by 3CDpro in vitro is dependent on the presence of a VPg-linked RNA template... - Complete protein linkage map between the P2 and P3 non-structural proteins of poliovirusJiang Yin
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
J Gen Virol 88:2259-67. 2007..The possible biological implication of the interactions observed in the yeast two-hybrid system will be discussed... - The C-terminal hydrophobic domain of hepatitis C virus RNA polymerase NS5B can be replaced with a heterologous domain of poliovirus protein 3AHaekyung Lee
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
J Virol 80:11343-54. 2006..This suggests that specific interactions between the NS5B hydrophobic domain and other membrane-bound factors may not play a decisive role in HCV replication... - Stimulation of poliovirus synthesis in a HeLa cell-free in vitro translation-RNA replication system by viral protein 3CDproDavid Franco
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11790, USA
J Virol 79:6358-67. 2005.... - Tyrosine 3 of poliovirus terminal peptide VPg(3B) has an essential function in RNA replication in the context of its precursor protein, 3ABYing Liu
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA
J Virol 81:5669-84. 2007.... - Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental eventSteffen Mueller
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA
Virus Res 111:175-93. 2005..This review will attempt to summarize our current knowledge of the molecular biology of poliovirus, its pathogenesis, as well as recent advances in the areas of cell and tissue tropism and mechanisms of central nervous system invasion... - Expression of the human poliovirus receptor/CD155 gene is activated by sonic hedgehogDavid J Solecki
Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, 11794, USA
J Biol Chem 277:25697-702. 2002..These data identify the CD155 gene as a transcriptional target of Shh, a finding that has significance for the normal function of CD155 during development and the expression of CD155 in neuroectodermal tumors... - Cis-acting RNA elements in human and animal plus-strand RNA virusesYing Liu
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11790, USA
Biochim Biophys Acta 1789:495-517. 2009.... - Recruitment of nectin-3 to cell-cell junctions through trans-heterophilic interaction with CD155, a vitronectin and poliovirus receptor that localizes to alpha(v)beta3 integrin-containing membrane microdomainsSteffen Mueller
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794, USA
J Biol Chem 278:31251-60. 2003.... - Characterization of the New World monkey homologues of human poliovirus receptor CD155Shaukat Khan
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794 5222, USA
J Virol 82:7167-79. 2008.... - Membrane topography of the hydrophobic anchor sequence of poliovirus 3A and 3AB proteins and the functional effect of 3A/3AB membrane association upon RNA replicationKentaro Fujita
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794 5222, USA
Biochemistry 46:5185-99. 2007..Moreover, in vitro uridylylation reactions showed that membrane-bound 3AB is not a substrate for 3D(pol), but free VPg released by cleavage of 3AB with proteinase 3CD(pro) could be uridylylated... - Replication of a novel subgenomic HCV genotype 1a replicon expressing a puromycin resistance gene in Huh-7 cellsChengyu Liang
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11790, USA
Virology 333:41-53. 2005..The data identify PAC as an efficient selectable marker for studies of HCV replication, which may be useful with different genotypes in different host cell systems...
Research Grants
- PICORNAVIRUS MOLECULAR BIOLOGYEckard Wimmer; Fiscal Year: 2010..Our understanding of the mechanism of encapsidation is expected to facilitate the development of new drugs to treat enteroviral infections. ..
- Evolution of Human C-cluster EnterovirusesEckard Wimmer; Fiscal Year: 2003..To assess this scenario we propose to establish a model system to test possibilities of speciation of C-cluster enteroviruses. ..
- EUROPIC america 2002: a conference for picornavirusesEckard Wimmer; Fiscal Year: 2002..The over will discuss the difficulties (circulation of vaccine strains, recent outbreak of poliomyelitis in the Western Hemisphere) that have emerged during the current, historic effect to globally eradicate poliovirus. ..
- POLIOVIRUS RECEPTOR AND INTERACTIONS WITH POLIOVIRUSEckard Wimmer; Fiscal Year: 2001..Finally, the genetic determinants of mouse neurovirulence of PV1(LS-a), a strain of poliovirus, will be studied with attention to genomic sequences outside the coding sequence for the capsid protein. ..
- Structure and Function of IRES ElementsEckard Wimmer; Fiscal Year: 2006..We will investigate the molecular reason for this attenuation. Finally, we will determine whether we can exchange viral IRESs also IRESs of cellular mRNA. ..
- Synthetic Viral Genome Design for Rapid Vaccine DevelopmentEckard Wimmer; Fiscal Year: 2010..We describe an entirely novel and rapid method to generate anti-virus vaccine candidates that might prove applicable to most if not all human pathogenic viral systems. ..
- Poliovirus Receptor and Poliovirus PathogenesisEckard Wimmer; Fiscal Year: 2009....
- Synthetic Viral Genome Design for Rapid Vaccine DevelopmentEckard Wimmer; Fiscal Year: 2009..We describe an entirely novel and rapid method to generate anti-virus vaccine candidates that might prove applicable to most if not all human pathogenic viral systems. ..
- PICORNAVIRUS MOLECULAR BIOLOGYEckard Wimmer; Fiscal Year: 2007..Our studies may lead to the development of new vaccines and of novel drugs directed against picornavirus infection...
- NOVEL CELLULAR REGULATORY FACTORS IN VIRAL TRANSLATIONEckard Wimmer; Fiscal Year: 2001..The tool for studying the HCV IRES will be a novel poliovirus/HCV chimeric virus whose translation is solely controlled by the HCV IRES. ..
- VIRAL ONCOLOGY: RETROVIRUSES AND POLIOVIRUSEckard Wimmer; Fiscal Year: 1980..This, we hope, will elucidate some key problems in the molecular biology of picornaviruses, namely, the nature of the ribosome attachment site and the mechanism of replication of viral RNA. ..
- NOVEL CELLULAR REGULATORY FACTORS IN VIRAL TRANSLATIONEckard Wimmer; Fiscal Year: 1993..They will also characterize cellular RNA binding proteins, a class of factors whose interaction with RNA and whose role in cellular metabolism is of central importance yet poorly understood...