Abstract

IRES elements are novel genetic elements identified in eukaryotic mRNA that regulate initiation of translation independently of a 5' end of a template. This research will continue studies on the structure and function of viral IRESes, particularly those of picornaviruses discovered in the P.I.s laboratory in 1987. As an extension of the previous aims, the P.I. will also study the IRES element of hepatitis C virus (HCV), an agent causing widespread disease world-wide. The P.I. will determine the parameters of tissue specific expression of IRES function, a project with specific reference to the neurovirulence character of picornaviruses. Moreover, he plans to dissect the structure/function relation of IRES elements of poliovirus, encephalomyocarditis virus (EMCV), and HCV with respect to cis-acting elements and trans-acting factors. The studies will be carried out by genetic manipulations of viral genomes, by a novel procedure called yeast three-hybrid system, and by molecular biological and biochemical procedures. The tool for studying the HCV IRES will be a novel poliovirus/HCV chimeric virus whose translation is solely controlled by the HCV IRES.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI032100-10
Application #
6341614
Study Section
Virology Study Section (VR)
Program Officer
Meegan, James M
Project Start
1992-01-01
Project End
2001-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
10
Fiscal Year
2001
Total Cost
$205,126
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

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; Wimmer, Eckard; Cello, Jeronimo (2005) Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. Virus Res 111:175-93
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

Showing the most recent 10 out of 39 publications