Curt M Horvath
Northwestern University
Project start date: 2001-12-01
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
Molecular Basis-Paramyxovirus-induced STAT Degradation
Curt M Horvath, Associate Professor
Evanston Northwestern Healthcare 2650 Ridge Avenue Evanston, Il 60201
Grant 5R01AI050707-06 from National Institute Of Allergy And Infectious Diseases IRG: EVR
Abstract: Type I interferons (IFN) are the principal antiviral cytokines and function directly on target cells by blocking virus replication. IFN signal transduction produces a transcriptional complex, ISGF3, that is composed of a DNA binding subunit in association with two proteins from the signal transducer and activator of transcription (STAT) family, STAT1 and STAT2. ISGF3 is the main effector of cellular IFN responses. The importance of IFN signaling in antiviral responses is underscored by the wide variety of strategies that viruses have evolved to evade IFN actions. The viral evasion mechanisms typically involve antagonism of antiviral enzymes that represent important potential targets for therapeutic intervention and rational drug design. The Paramyxoviridae family of negative-strand RNA viruses includes several well known human pathogens like measles, mumps, respiratory syncytial, and human parainfluenza viruses. Recent findings from the PI s own lab and others indicate that a subset of paramyxoviruses can evade IFN antiviral responses by targeting the STAT protein components of ISGF3 for proteolytic degradation. This STAT protein degradation is mediated by expression of a single viral gene coding for the V protein. Two different paramyxoviruses, simian virus 5 (SV5) and human parainfluenza virus type 2 (HPIV2), evade IFN by targeting the ISGF3 transcription complex, but while the SV5 V protein mediates destruction of STAT1, the HPIV2 V protein mediates destruction of STAT2. The hypothesis that the specificity of V protein-induced STAT recognition and degradation is mediated by discrete protein segments and that V proteins must enlist cellular proteolytic machinery to target specific STAT proteins for proteolysis will be investigated. Chimeric V proteins and STAT proteins will be used in degradation assays to determine the molecular basis for selectivity and specificity in the V protein mediated STAT targeting. V protein-induced modifications of themselves and the STAT targets by ubiquitin and similar ligands will be directly examined in mammalian cells and in vitro ubiquitination assays. GST fusion protein affinity chromatography and immuno-affinity purification strategies will be used to define the cellular machinery involved in this reaction. Together, these experiments will reveal the mechanisms and cellular apparatus used by the paramyxovirus proteins to target and degrade STAT proteins and evade IFN actions.
Keywords: Paramyxoviridae, interferon, protein degradation, transcription factor, virus infection mechanism, virus protein, chimeric protein, parainfluenza virus type 2, simian virus, ubiquitin, affinity chromatography, clinical research, tissue /cell culture
Project start date: 2002-07-01
Project end date: 2008-01-14
5R01AI050707-06 (2006): $296856
5R01AI050707-05 (2005): $304000
5R01AI050707-03 (2004): $12424
5R01AI050707-02 (2003): $332050
MOLECULAR BASIS OF PARAMYXOVIRUS-INDUCED STAT DEGRADATION
Curt M Horvath
Northwestern University, Evanston, Il 60208-1110
Grant 5R01AI050707-10 from National Institute Of Allergy And Infectious Diseases
Keywords: Address; Animal Welfare; Antiviral Agents; Antiviral Drugs; Antivirals; Bibliography; Biology; Bypass; Cell Communication and Signaling; Cell Signaling; Commit; Country; Critiques; Ecological impact; Educational process of instructing; Elements; Environment; Environmental Impact; Epidemic Parotitis Virus; Equipment; Ethics Committees, Research; Family; Future; Genetic Alteration; Genetic Change; Genetic defect; Health; Host Defense; Human; Human, General; IACUC; IFN; IRBs; ISFG-3; ISGF-3; Immune response; Impact, Environmental; Industry; Institutional Animal Care and Use Committee; Institutional Review Boards; Interferon Type I; Interferons; International; Intracellular Communication and Signaling; Literature; Man (Taxonomy); Man, Modern; Measles; Measles virus; Molecular; Molecular Analysis; Mumps; Mumps virus; Mutation; Myxovirus parotitidis; Northern Ireland; Outcome; P113; Paramyxovirus; Parotitis, Epidemic; Principal Investigator; Programs (PT); Programs [Publication Type]; Proteins; RNA Viruses; Research; Research Ethics Committees; Research Resources; Resources; Role; Rubeola; STAT protein; STAT1; STAT1 gene; STAT113; STAT2; STAT2 gene; STAT3; STAT3 gene; STAT91; Science of Virology; Signal Transducer and Activator of Transcription; Signal Transduction; Signal Transduction Systems; Signaling; System; System, LOINC Axis 4; Teaching; Therapeutic; V protein, HPIV2; V protein, Human parainfluenza virus 2; V protein, hPIV-2; Vertebrate Animals; Vertebrates; Viral; Viral Diseases; Virology; Virus; Virus Diseases; Virus Replication; Viruses, General; Work; Writing; ing; base; biological signal transduction; epidemic parotiditis; expiration; gene product; genome mutation; hPIV-2 V protein; high standard; host response; human subject; immunoresponse; inhibitor; inhibitor/antagonist; interest; meetings; morbilli; novel; pathogen; positional cloning; programs; response; reverse genetics; rougeole virus; rubeola virus; social role; vertebrata; viral infection; virology; virus infection; virus multiplication
Project start date: 2001-12-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2010
Budget end date: 31-DEC-2010
PFA/PA: PA-07-246
5R01AI050707-10 (2010): $303763
Grants awarded to Curt M Horvath
Molecular Basis-Paramyxovirus-induced STAT Degradation
Curt M Horvath, Associate Professor
Evanston Northwestern Healthcare 2650 Ridge Avenue Evanston, Il 60201
Grant 7R01AI050707-04 from National Institute Of Allergy And Infectious Diseases IRG: EVR
Abstract: Type I interferons (IFN) are the principal antiviral cytokines and function directly on target cells by blocking virus replication. IFN signal transduction produces a transcriptional complex, ISGF3, that is composed of a DNA binding subunit in association with two proteins from the signal transducer and activator of transcription (STAT) family, STAT1 and STAT2. ISGF3 is the main effector of cellular IFN responses. The importance of IFN signaling in antiviral responses is underscored by the wide variety of strategies that viruses have evolved to evade IFN actions. The viral evasion mechanisms typically involve antagonism of antiviral enzymes that represent important potential targets for therapeutic intervention and rational drug design. The Paramyxoviridae family of negative-strand RNA viruses includes several well known human pathogens like measles, mumps, respiratory syncytial, and human parainfluenza viruses. Recent findings from the PI s own lab and others indicate that a subset of paramyxoviruses can evade IFN antiviral responses by targeting the STAT protein components of ISGF3 for proteolytic degradation. This STAT protein degradation is mediated by expression of a single viral gene coding for the V protein. Two different paramyxoviruses, simian virus 5 (SV5) and human parainfluenza virus type 2 (HPIV2), evade IFN by targeting the ISGF3 transcription complex, but while the SV5 V protein mediates destruction of STAT1, the HPIV2 V protein mediates destruction of STAT2. The hypothesis that the specificity of V protein-induced STAT recognition and degradation is mediated by discrete protein segments and that V proteins must enlist cellular proteolytic machinery to target specific STAT proteins for proteolysis will be investigated. Chimeric V proteins and STAT proteins will be used in degradation assays to determine the molecular basis for selectivity and specificity in the V protein mediated STAT targeting. V protein-induced modifications of themselves and the STAT targets by ubiquitin and similar ligands will be directly examined in mammalian cells and in vitro ubiquitination assays. GST fusion protein affinity chromatography and immuno-affinity purification strategies will be used to define the cellular machinery involved in this reaction. Together, these experiments will reveal the mechanisms and cellular apparatus used by the paramyxovirus proteins to target and degrade STAT proteins and evade IFN actions.
Keywords: Paramyxoviridae, interferon, protein degradation, transcription factor, virus infection mechanism, virus protein, chimeric protein, parainfluenza virus type 2, simian virus, ubiquitin, affinity chromatography, clinical research, tissue /cell culture
Project start date: 2002-07-01
Project end date: 2007-06-30
7R01AI050707-04 (2004): $292858
1R01AI050707-01A1 (2002): $332050
Mediators Of Interferon-Mediated Gene Expression
Curt M Horvath, Associate Professor
Evanston Northwestern Healthcare 2650 Ridge Avenue Evanston, Il 60201
Grant 5R01GM063872-05 from National Institute Of General Medical Sciences IRG: ZRG1
Abstract: Treatment of cells with type I interferon (IFN) leads to transcriptional activation of genes involved in cellular antiviral effects, growth inhibition, and immune regulation. The study of IFN-mediated transcription is critical to treatment of chronic viral diseases including HIV, the causative agent of AIDS and Hepatitis C, the leading cause of liver failure and cirrhosis. Both viruses are endemic in the United States and IFN has been used in their treatment. The long term objective of my laboratory is to understand the mechanisms by which STAT and IRF transcription factors combine to produce the trimeric IFN-responsive transcription complex, ISGF3. The ISGF3 factor is a unique STAT-dependent transcription complex because the signaling phase is dissociated from the nuclear functions by an obligatory DNA binding subunit, IRF9/p48. Although the signal transduction pathways involved in activation of the ISGF3 trimeric transcription factor complex have been well studied, the mechanism of transcriptional activation is only poorly understood. The published literature and our own preliminary studies indicate that a fundamental transcriptional activation domain (TAD) for ISGF3 resides in the STAT2 C-terminus. Preliminary studies using IRF9-STAT2 TAD fusion proteins that mimic ISGF3 transcriptional responses and recapitulate IFN biological responses have produced a structure-function map of this domain and have contributed to generating the hypothesis that the STAT2 TAD provides a protein interaction platform for several types of transcriptional co-activators. In support of this hypothesis, we have used a candidate-partner approach to identify a new transcriptional partner for STAT2 that is a subunit of the metazoan Mediator complex. Analysis of endogenous ISGF3 activity in STAT2 mutant-expressing cell lines will be carried out to connect specific STAT2 TAD regions with specific target gene expression patterns, biological responses, and promoter chromatin remodeling activities. The four proposed experimental aims will (1) determine the functional significance of transcriptionally important STAT2 C-terminal TAD regions in a physiological context, (2) characterize the molecular mechanisms involved in STAT2 interactions with Mediator subunits, (3) determine the ability of ISGF3 to regulate promoter chromatin dynamics and map corresponding STAT2 C-terminal regions, and (4) identify additional protein partners for the STAT2 C-terminus. The proposed experiments provide a unique model system for the study of activated transcription, in which contributions of specific STAT2 TAD regions responsible for IFN target gene expression patterns, co-activator recruitment, and/or chromatin remodeling activities can be correlated with physiologically relevant IFN biological responses.
Keywords: gene expression, interferon, protein protein interaction, protein structure function, transcription factor, chimeric protein, chromatin, gene mutation, genetic model, genetic regulatory element, affinity chromatography, cell line, clinical research, immunoprecipitation
Project start date: 2003-07-01
Project end date: 2008-06-30
5R01GM063872-05 (2006): $267170
5R01GM063872-04 (2005): $273600
7R01GM063872-03 (2004): $240631
5R01GM063872-02 (2004): $36765
1R01GM063872-01A2 (2003): $298845
Crosstalk In RNA Mediated Innate Antiviral Responses
Curt M Horvath, Associate Professor
Evanston Northwestern Healthcare
2650 Ridge Avenue
evanston, Il 60201
Grant 5R21AI077020-02 from National Institute Of Allergy And Infectious Diseases IRG: ZAI1
Abstract: The virulence of influenza virus strains has been linked to their ability to disengage cellular innate antiviral responses. One current antiviral therapeutic strategy for emerging influenza strains involves the use of RNA silencing techniques, and this approach has already shown great promise in the treatment of influenza virus infections. This proposal is designed to use influenza virus infections as a means to explore the interaction and crosstalk between two innate antiviral systems triggered by intracellular double stranded RNA (dsRNA). RNA interference (RNAi) is an intrinsic dsRNA-mediated gene silencing system that is central to cellular gene regulation in the plant and animal kingdoms. RNAi is a potent innate antiviral system central to pathogen defenses in plants and lower animals, and has been harnessed as a therapeutic strategy for human diseases. In vertebrates, the type I interferons induce a potent cellular antiviral response. The IFN genes originated by duplication of a progenitor after the divergence of birds approximately 250 million years ago. The antiviral contributions of RNA silencing are less pronounced in vertebrates, and dsRNA based innate immune response genes may have arisen from components of the RNA silencing system. It is the central hypothesis underlying this proposal is that these two ancient dsRNA processing systems are functionally integrated in the regulation of cellular innate antiviral immune responses in human cells. The interdependence and cross-regulation between these two RNA processing systems is the focus of this exploratory application. Two complementary specific aims are proposed to test the link between IFN antiviral signaling and RNA silencing in the context of influenza virus infections
Project start date: 2007-08-15
Project end date: 2009-07-31
5R21AI077020-02 (2008): $187003
7R21AI077020-03 (2008): $0
1R21AI077020-01 (2007): $228750
Sponsored Links Excellgen http://Excellgen.com
New Paradigms In Gene Regulation During Influenza Virus Infections
Curt M Horvath, Associate Professor
Evanston Northwestern Healthcare
Grant 1U01AI082984-01 from National Institute Of Allergy And Infectious Diseases IRG: ZAI1
Abstract: The long term objective for this project is to understand the regulatory mechanisms and specific mediators of innate antiviral responses in human lung cells following influenza virus infections. Much is known in general about cellular virus detection by the innate immune system and the inducible gene expression events that accompany the acquisition of cellular and systemic responses. However, individual hosts can demonstrate variability in resistance to infection in a virus-specific or cell-specific fashion. These differential responses are the result of many factors including variable transcriptional responses or post- transcriptional regulation of gene expression at the primary site of infection. This application is designed to elucidate new paradigms for innate cellular responses to influenza virus infection with both basic research and clinical approaches. One specific aim will examine the hypothesis that post-transcriptional gene regulation modulates canonical antiviral gene expression programs during influenza infections, and will decipher the roles of cytokine- and virus-induced microRNAs by examining their biogenesis and activity in infected lung cell lines. A second aim will test the hypothesis that differential gene expression in the airway mucosa, the main site of influenza virus infection, relates to severity of clinical presentation of human influenza. Transcriptomes of airway mucosal samples will be analyzed during acute phase and convalescence of human influenza infections to identify novel gene expression patterns and pathways related to severe influenza infections. In addition, comparison of airway mucosal transcriptomes between those predisposed to severe influenza and those who experienced milder disease will identify novel gene expression patterns and pathways related to susceptibility to influenza infections. Together these aims will elucidate new fundamental innate immune mechanisms, provide a more sophisticated understanding of the antiviral response, and potential new targets for antiviral therapy
Project start date: 2009-05-01
Project end date: 2014-04-30
7U01AI082984-02 (2009): $756534
Host Defense Evasion By Fatal Emerging Paramyxoviruses
Curt M Horvath, Associate Professor
Evanston Northwestern Healthcare
2650 Ridge Avenue
evanston, Il 60201
Grant 5R01AI055733-06 from National Institute Of Allergy And Infectious Diseases IRG: ZRG1
Abstract: The ability of enveloped negative strand RNA viruses of the family Paramyxoviridae to rapidly disseminate throughout a broad range of host species is often a cause of fatal diseases. The threat to humans and animals posed by these viruses is well illustrated by recent outbreaks of fatal encephalitis in southeast Asia and Australia resulting from the previously unrecognized Paramyxoviruses, Nipah virus and Hendra virus. Within the Paramyxoviridae, many criteria have distinguished Nipah and Hendra viruses as representative of a new genus, Henipavirus. One genomic feature that positively links them to other paramyxoviruses is a conserved cysteine-rich protein domain that is the hallmark of paramyxovirus ´V´ proteins. The V proteins of other paramyxoviruses have been linked to evasion of host interferon (IFN) signal transduction and subsequent innate antiviral responses, by inducing proteasomal degradation of the IFN-responsive transcription factors, STAT1 or STAT2. Preliminary investigations demonstrate that the Nipah virus V protein evades host IFN-activated defenses by a different mechanism. Nipah virus V protein does not induce STAT protein degradation, but instead induces formation of high molectflar weight cytoplasmic complexes that contain STAT1 and STAT2. Thus, Nipah virus V protein expression alters STAT subcellular distribution in the steady-state, prevents IFNstimulated STAT tyrosine phosphorylation, and blocks IFN-induced STAT nuclear relocalization, resulting in inhibition of cellular responses to either IFNalpha/beta or IFNgamma. The V protein is situated at the paramyxovirus-host interface and is not only a potential pathogenesis-determining factor, but also represents a therapeutic target for pharmaceutical intervention and vaccine development, contributing to an armamentarium for the control of natural outbreaks or bioterrorist threats. The molecular basis for Henipavirus V protein anti-cellular functions will be investigated with three aims to (i) Determine the ability of Hendra virus V protein to prevent STAT function in WN signal transduction (ii) Define critical functional domains involved in Henipavirus IFN evasion and subcellular distribution, and (iii) Characterize components and assemble of V protein-induced IFN evasion complexes
Keywords: Paramyxoviridae, emerging infectious disease, host organism interaction, protein structure function, virus infection mechanism, virus protein Nipah virus, biological signal transduction, equine morbillivirus, interferon, protein protein interaction, transcription factor SDS polyacrylamide gel electrophoresis, affinity chromatography, clinical research, electrospray ionization mass spectrometry, high performance liquid chromatography, immunoprecipitation, polymerase chain reaction, site directed mutagenesis
Project start date: 2004-02-15
Project end date: 2010-01-31
5R01AI055733-06 (2008): $247424
5R01AI055733-05 (2007): $252217
5R01AI055733-04 (2006): $259750
5R01AI055733-03 (2005): $266000
7R01AI055733-02 (2004): $201066
1R01AI055733-01A1 (2004): $72410
Type 1 Interferon In Innate And Adaptive Virus Immunity
Curt M Horvath, Associate Professor
Center For Immunobiologymount Sinai School Of Medicine Of Nyu
of New York University
new York, Ny 100296574
Grant 1R21AI048722-01A1 from National Institute Of Allergy And Infectious Diseases IRG: ZRG1
Abstract: Effective immunity to virus infection involves both innate and adaptive host responses. Interferons (IFNs) have long been widely recognized as critical mediators of innate antiviral responses. Type I IFNs, IFNa and IFNb, are the principle antiviral cytokines produced by mammalian cells and function directly on target cells by blocking virus replication. Recently, it has become apparent that type I IFNs may also play a role in adaptive immune responses including T lymphocyte maturation, survival, and immunological memory. The regulation of interferon-inducible transcriptional responses which lead to both innate and adaptive antiviral immunity will be investigated. To better understand the role of Type I IFN in regulating both innate and adaptive antiviral responses, the fundamental molecular mechanisms underlying activation of gene expression by the ISGF3 (interferon stimulated gene factor 3) complex will be studied. The transcriptional activity of the ISGF3 subunits will be dissected biochemically using a newly developed hybrid transcription factor approach. Cellular proteins involved in mediating transcription by ISGF3 will be identified and characterized in transcriptional assays. The hybrid IFN transcription factors will be tested for the ability to establish innate antiviral states in cultured cells and tested for their ability to influence T cell signaling and survival in culture. The role of constitutive Type I IFN responsive transcription mediated by the hybrid IFN transcription factors in bridging innate and adaptive antiviral immune responses will be investigated directly in T lymphocyte specific transgenic mouse models. The studies in this application will (i.) provide a biochemical basis for ISGF3 transcriptional activity, (ii.) will directly test the link between innate and adaptive antiviral effects of ISGF3-dependent transcription, and (iii.) will validate the role of IFN in mediating T cell responses in vivo. Successful completion of these studies should greatly enhance our knowledge of cytokine effects on antiviral immune responses
Keywords: chimeric protein, interferon alpha, interferon beta, microorganism immunology, transcription factor T lymphocyte, gene expression, genetic promoter element, genetic transcription, immunologic memory, reporter gene, virus replication SDS polyacrylamide gel electrophoresis, biotechnology, cell line, cell mediated lymphocytolysis test, enzyme linked immunosorbent assay, flow cytometry, laboratory mouse, polymerase chain reaction, radioimmunoassay, transgenic animal
Project start date: 2001-09-30
Project end date: 2002-09-29
1R21AI048722-01A1 (2001): $339000
Type I Interferon In Innate And Adaptive Virus Immunity
Curt M Horvath, Associate Professor
Evanston Northwestern Healthcare 2650 Ridge Avenue Evanston, Il 60201
Grant 5R01AI048722-05 from National Institute Of Allergy And Infectious Diseases IRG: ZRG1
Abstract: Effective immunity to virus infection involves both innate and adaptive host responses. Interferons (IFNs) have long been widely recognized as critical mediators of innate antiviral responses. Type I IFNs, IFNA and IFNB, are the principal antiviral cytokines produced by mammalian cells and function directly on target cells by blocking virus replication. Recently, it has become apparent that type I IFNs may also play a role in adaptive immune responses including T lymphocyte maturation and differentiation, survival, and immunological memory. The regulation of interferon-inducible transcriptional responses which lead to both innate and adaptive antiviral immunity will be investigated. To better understand the role of Type I IFN in regulating both innate and adaptive antiviral responses, the fundamental molecular mechanisms underlying activation of gene expression by the ISGF3 (interferon stimulated gene factor 3) complex will be studied. The transcriptional activity of the ISGF3 subunits will be dissected biochemically using a newly developed hybrid transcription factor approach. Cellular proteins involved in mediating transcription by ISGF3 will be identified and characterized in transcriptional assays. The hybrid IFN transcription factors will be tested for the ability to establish innate antiviral states in cultured cells and tested for their ability to influence T cell signaling and survival in culture. Results of these experiments will be verified in the context of intact IFN signaling. The effects of Type I IFN and the responses initiated by the hybrid IFN transcription factors will be investigated directly in T lymphocytes. The studies in this proposal will provide a biochemical basis for ISGF3 transcriptional activity, test the relationship between innate antiviral effects of ISGF3-induced transcription and adaptive responses to IFN signals, and validate the emerging role of IFN in mediating T cell responses. Successful completion of these studies will greatly enhance our knowledge of cytokine effects on antiviral immune responses.
Keywords: chimeric protein, immunity, interferon alpha, interferon beta, transcription factor, T cell receptor, T lymphocyte, biological signal transduction, cytokine, gene expression, genetic promoter element, genetic transcription, immunologic memory, reporter gene, virus replication, clinical research, clone cell, enzyme linked immunosorbent assay, microarray technology, polymerase chain reaction, tissue /cell culture, transfection
Project start date: 2002-06-01
Project end date: 2007-05-31
5R01AI048722-05 (2005): $304000
Sponsored Links Excellgen http://Excellgen.com
7R01AI048722-04 (2004): $263880
5R01AI048722-03 (2004): $44739
5R01AI048722-02 (2003): $339000
Curt M Horvath
Northwestern University
Project start date: 2007-12-15
Project end date: 2012-11-30
HELICASE REGULATION OF DSRNA SIGNALING AND INNATE ANTIVIRAL IMMUNE RESPONSES
Curt M Horvath
Northwestern University, Evanston, Il 60208-1110
Grant 5R01AI073919-04 from National Institute Of Allergy And Infectious Diseases
Keywords: A549; Address; Anabolism; Animal Welfare; Anti-Viral Response; Antiviral Agents; Antiviral Drugs; Antiviral Response; Antivirals; Baculoviruses; Bibliography; Biochemical; Biological; Boxing; Cell Communication and Signaling; Cell Culture Techniques; Cell Signaling; Cells; Comment; Comment (PT); Comment [Publication Type]; Commentary; Commentary (PT); Country; Critiques; DNA Helicases; DNA Unwinding Proteins; DNA unwinding enzyme; Detection; Double-Stranded RNA; Ecological impact; Editorial Comment; Editorial Comment (PT); Environment; Environmental Impact; Equipment; Ethics Committees, Research; Evaluation; Exhibits; Family; Feedback; Gene Products, RNA; Hand; Hepatic Cells; Hepatic Parenchymal Cell; Hepatocyte; Human; Human, General; IACUC; IFN; IRBs; Immune response; Impact, Environmental; In Vitro; Institutional Animal Care and Use Committee; Institutional Review Boards; Interferon Type I; Interferons; International; Intracellular Communication and Signaling; Investigation; Knock-out; Knockout; Literature; Liver Cells; Lung Adenocarcinoma; Man (Taxonomy); Man, Modern; Mediating; Mediator; Mediator of Activation; Mediator of activation protein; Molecular; N-terminal; NH2-terminal; Paramyxovirus; Pathway interactions; Peptide Domain; Post-Transcriptional Gene Silencing; Post-Transcriptional Gene Silencings; Posttranscriptional Gene Silencing; Posttranscriptional Gene Silencings; Principal Investigator; Production; Programs (PT); Programs [Publication Type]; Protein Domains; Proteins; Published Comment; Publishing; Quelling; RNA; RNA Helicase; RNA Interference; RNA Silencing; RNA Silencings; RNA, Double-Stranded; RNA, Non-Polyadenylated; RNAi; Regulation; Relative; Relative (related person); Reporting; Research; Research Ethics Committees; Research Resources; Resources; Respiratory Infections; Respiratory Tract Infections; Ribonucleic Acid; Role; Sequence-Specific Posttranscriptional Gene Silencing; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Signaling Protein; Specificity; System; System, LOINC Axis 4; TLR protein; TLR3; TLR3 gene; Tertiary Protein Structure; Toll-like receptors; Vertebrate Animals; Vertebrates; Viewpoint; Viewpoint (PT); Viral Diseases; Viral Pathogenesis; Virus Diseases; Virus Replication; ing; base; biological signal transduction; biosynthesis; dsRNA; experiment; experimental research; experimental study; expiration; falls; fibrosarcoma; gene product; helicase; host response; human subject; immunoresponse; in vivo; inhibitor; inhibitor/antagonist; interest; pathway; preference; programs; protein purification; research study; response; sensor; social role; tool; vertebrata; viral infection; virus infection; virus multiplication
Project start date: 2007-12-15
Project end date: 2012-11-30
Budget start date: 1-DEC-2009
Budget end date: 30-NOV-2010
PFA/PA: PA-07-070
5R01AI073919-04 (2010): $347744
CLONING OF GROWTH FACTOR SECOND MESSENGERS
Curt M Horvath, Associate Professor
Lab Of Molecular Cell Biologyrockefeller University
new York, Ny 100656399
Grant 5F32NS009230-03 from National Institute Of Neurological Disorders And Stroke IRG: BIOL
5F32NS009230-03 (1994): $23700