Abstract

An Internal Ribosomal Entry Site (IRES) is a genetic element found in the genome of certain eukaryotic plus strand RNA viruses and cellular mRNAs. IRESs direct attachment of the 30S ribosomal subunit to a site downstream of the commonly used 5'terminal cap. IRES elements are large segments of RNA of different sequence that are highly structured. Neither the precise structure of these elements nor the precise mode of function is known. In this application, we propose to study the structure of the IRES of hepatitis C virus with respect structure and function. Furthermore, we will attempt to decipher the role of RNA binding proteins in the function of picornavirus and HCV IRES function. We have previously observed that an exchange of the poliovirus IRES element with that of rhinovirus type 2 results in a chimera, expressing an attenuated neurovirulence phenotype. We will investigate the molecular reason for this attenuation. Finally, we will determine whether we can exchange viral IRESs also IRESs of cellular mRNA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI032100-15
Application #
7005400
Study Section
Virology Study Section (VR)
Program Officer
Koshy, Rajen
Project Start
1992-01-01
Project End
2006-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
15
Fiscal Year
2006
Total Cost
$257,186
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Genetics
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Mueller, Steffen; Wimmer, Eckard; Cello, Jeronimo (2005) Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. Virus Res 111:175-93
Liang, Chengyu; Rieder, Elizabeth; Hahm, Bumsuk et al. (2005) Replication of a novel subgenomic HCV genotype 1a replicon expressing a puromycin resistance gene in Huh-7 cells. Virology 333:41-53
Mueller, Steffen; Cao, Xuemei; Welker, Reinhold et al. (2002) Interaction of the poliovirus receptor CD155 with the dynein light chain Tctex-1 and its implication for poliovirus pathogenesis. J Biol Chem 277:7897-904
Pfister, Thomas; Feng, Huan; Wimmer, Eckard et al. (2002) Synchrotron radiation-induced X-ray emission to identify metal ions in preparations of purified protein. Biotechniques 32:134-6, 138, 140-1
Li, X; Lu, H H; Mueller, S et al. (2001) The C-terminal residues of poliovirus proteinase 2A(pro) are critical for viral RNA replication but not for cis- or trans-proteolytic cleavage. J Gen Virol 82:397-408
Pfister, T; Wimmer, E (2001) Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent nucleoside triphosphatase. J Virol 75:1611-9
Xiao, C; Bator, C M; Bowman, V D et al. (2001) Interaction of coxsackievirus A21 with its cellular receptor, ICAM-1. J Virol 75:2444-51
Pfister, T; Jones, K W; Wimmer, E (2000) A cysteine-rich motif in poliovirus protein 2C(ATPase) is involved in RNA replication and binds zinc in vitro. J Virol 74:334-43
Zhao, W D; Lahser, F C; Wimmer, E (2000) Genetic analysis of a poliovirus/hepatitis C virus (HCV) chimera: interaction between the poliovirus cloverleaf and a sequence in the HCV 5' nontranslated region results in a replication phenotype. J Virol 74:6223-6
Zhao, W D; Wimmer, E; Lahser, F C (1999) Poliovirus/Hepatitis C virus (internal ribosomal entry site-core) chimeric viruses: improved growth properties through modification of a proteolytic cleavage site and requirement for core RNA sequences but not for core-related polypeptides. J Virol 73:1546-54

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