Abstract

The aim of this research is to understand the mechanism by which poliovirus infection causes a specific inhibition of host cell protein synthesis while production of viral proteins proceeds efficiently. Infected cell extracts show a loss of the ability to translate capped mRNAs in vitro, although they do function in the translation of viral RNA. This is due to a virus-induced inactivation of a specific translational initiation factor (the cap binding protein complex) which recognizes and binds the 5' cap group on cellular mRNAs, and seems to facilitate the binding of mRNA to the 40S ribosomal subunit. Poliovirus mRNA is not capped and, therefore, presumably can by-pass the requirement for the cap binding protein. Studies proposed in this application will define the biochemical mechanism of the inactivation of cap binding activity, and will result in the purification and identification of the viral mediator of the inactivation reaction. Additional studies are proposed to define the mechanism of ribosome binding and initiation of translation of poliovirus mRNA, which occurs in the absence of a cap group.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012387-14
Application #
3125176
Study Section
Experimental Virology Study Section (EVR)
Project Start
1975-05-01
Project End
1990-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
14
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Walter, B L; Nguyen, J H; Ehrenfeld, E et al. (1999) Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements. RNA 5:1570-85
Stewart, S R; Semler, B L (1998) RNA structure adjacent to the attenuation determinant in the 5'-non-coding region influences poliovirus viability. Nucleic Acids Res 26:5318-26
Graff, J; Ehrenfeld, E (1998) Coding sequences enhance internal initiation of translation by hepatitis A virus RNA in vitro. J Virol 72:3571-7
Graff, J; Cha, J; Blyn, L B et al. (1998) Interaction of poly(rC) binding protein 2 with the 5' noncoding region of hepatitis A virus RNA and its effects on translation. J Virol 72:9668-75
Blyn, L B; Towner, J S; Semler, B L et al. (1997) Requirement of poly(rC) binding protein 2 for translation of poliovirus RNA. J Virol 71:6243-6
Davis, H L; McCluskie, M J; Gerin, J L et al. (1996) DNA vaccine for hepatitis B: evidence for immunogenicity in chimpanzees and comparison with other vaccines. Proc Natl Acad Sci U S A 93:7213-8
Blyn, L B; Swiderek, K M; Richards, O et al. (1996) Poly(rC) binding protein 2 binds to stem-loop IV of the poliovirus RNA 5' noncoding region: identification by automated liquid chromatography-tandem mass spectrometry. Proc Natl Acad Sci U S A 93:11115-20
Ehrenfeld, E; Semler, B L (1995) Anatomy of the poliovirus internal ribosome entry site. Curr Top Microbiol Immunol 203:65-83
Blyn, L B; Chen, R; Semler, B L et al. (1995) Host cell proteins binding to domain IV of the 5' noncoding region of poliovirus RNA. J Virol 69:4381-9
Harmon, S A; Emerson, S U; Huang, Y K et al. (1995) Hepatitis A viruses with deletions in the 2A gene are infectious in cultured cells and marmosets. J Virol 69:5576-81

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