Abstract
A cornerstone of the antiviral interferon response is phosphorylation of eukaryotic initiation factor (eIF)2α. This limits the availability of eIF2·GTP·Met-tRNAiMetternary complexes, reduces formation of 43S preinitiation complexes, and blocks viral (and most cellular) mRNA translation. However, many viruses have developed counterstrategies that circumvent this cellular response. Herein, we characterize a novel class of translation initiation inhibitors that block ternary complex formation and prevent the assembly of 43S preinitiation complexes. We find that translation driven by the HCV IRES is refractory to inhibition by these compounds at concentrations that effectively block cap-dependent translation in vitro and in vivo. Analysis of initiation complexes formed on the HCV IRES in the presence of inhibitor indicates that eIF2α and Met-tRNAiMetare present, defining a tactic used by HCV to evade part of the antiviral interferon response.
Bibliography
Robert, F., Kapp, L. D., Khan, S. N., Acker, M. G., Kolitz, S., Kazemi, S., Kaufman, R. J., Merrick, W. C., Koromilas, A. E., Lorsch, J. R., & Pelletier, J. (2006). Initiation of Protein Synthesis by Hepatitis C Virus Is Refractory to Reduced eIF2 · GTP · Met-tRNAiMetTernary Complex Availability. Molecular Biology of the Cell, 17(11), 4632â4644.
Authors
11
- Francis Robert (first)
- Lee D. Kapp (additional)
- Shakila N. Khan (additional)
- Michael G. Acker (additional)
- Sarah Kolitz (additional)
- Shirin Kazemi (additional)
- Randal J. Kaufman (additional)
- William C. Merrick (additional)
- Antonis E. Koromilas (additional)
- Jon R. Lorsch (additional)
- Jerry Pelletier (additional)
References
49
Referenced
106
10.1073/pnas.94.6.2249
/ Proc. Natl. Acad. Sci. USA by Ali N. (1997)10.1074/jbc.M006343200
/ J. Biol. Chem by Anwar A. (2000)10.1016/S0021-9258(18)50744-4
/ J. Biol. Chem by Benne R. (1979)10.1016/S0021-9258(17)40805-2
/ J. Biol. Chem by Benne R. (1978)10.1016/j.str.2005.08.008
/ Structure by Boehringer D. (2005)10.1126/science.1101902
/ Science by Boyce M. (2005)10.1093/nar/26.13.3179
/ Nucleic Acids Res by Buratti E. (1998){'key': 'B8', 'first-page': '853', 'volume': '14', 'author': 'Catchpoole D. R.', 'year': '1994', 'journal-title': 'Anticancer Res'}
/ Anticancer Res by Catchpoole D. R. (1994)10.1128/MCB.24.15.6861-6870.2004
/ Mol. Cell. Biol by Costa-Mattioli M. (2004)10.1074/jbc.M109199200
/ J. Biol. Chem by Fernandez J. (2002)10.1074/jbc.M201052200
/ J. Biol. Chem by Fernandez J. (2002)10.1128/MCB.18.9.5208
/ Mol. Cell. Biol by Gale M. (1998)10.1093/nar/4.9.3055
/ Nucleic Acids Res by Hallick R. B. (1977)- Hinnebusch A. G. (2000). Mechanism and Regulation of Initiator Methionyl-tRNA Binding to Ribosomes In: Cold Spring Harbor, NY: Cold Spring Harbor Press.
10.1074/jbc.M305038200
/ J. Biol. Chem by Hui D. J. (2003)10.1016/S0022-2836(02)01099-9
/ J. Mol. Biol by Jan E. (2002)10.1073/pnas.0407402101
/ Proc. Natl. Acad. Sci. USA by Ji H. (2004)10.1016/j.jmb.2003.11.025
/ J. Mol. Biol by Kapp L. D. (2004)10.1128/MCB.24.8.3415-3429.2004
/ Mol. Cell. Biol by Kazemi S. (2004){'key': 'B20', 'first-page': '370', 'volume': '9', 'author': 'Kieft J. S.', 'year': '2002', 'journal-title': 'Nat. Struct. Biol'}
/ Nat. Struct. Biol by Kieft J. S. (2002)10.1017/S1355838201001790
/ RNA by Kieft J. S. (2001)10.1128/JVI.74.14.6242-6250.2000
/ J. Virol by Kolupaeva V. G. (2000)10.1074/jbc.M413728200
/ J. Biol. Chem by Komar A. A. (2005)10.1128/MCB.7.10.3438
/ Mol. Cell. Biol by Kozak M. (1987){'key': 'B25', 'first-page': '1', 'author': 'Lancaster A. M.', 'year': '2006', 'journal-title': 'RNA'}
/ RNA by Lancaster A. M. (2006)10.1093/emboj/18.23.6705
/ EMBO J by Lorsch J. R. (1999)10.1128/JVI.75.16.7629-7636.2001
/ J. Virol by Lytle J. R. (2001)10.1017/S1355838202029965
/ RNA by Lytle J. R. (2002)10.1016/j.molcel.2004.11.051
/ Mol. Cell by Maag D. (2005)10.1006/mthe.2000.0050
/ Mol. Ther by Mizuguchi H. (2000)10.1093/nar/gkh235
/ Nucleic Acids Res by Novac O. (2004)10.1016/j.cell.2004.09.038
/ Cell by Otto G. A. (2004)10.1101/gad.1040803
/ Genes Dev by Pestova T. V. (2003)10.1128/MCB.16.12.6859
/ Mol. Cell. Biol by Pestova T. V. (1996)10.1038/sj.embor.7400240
/ EMBO Rep by Pestova T. V. (2004)10.1101/gad.12.1.67
/ Genes Dev by Pestova T. V. (1998)10.1073/pnas.062055699
/ Proc. Natl. Acad. Sci. USA by Pflugheber J. (2002)10.1016/S1097-2765(01)00265-9
/ Mol. Cell by Scheuner D. (2001)10.1128/JVI.72.6.4775-4782.1998
/ J. Virol by Sizova D. V. (1998)10.1126/science.1058409
/ Science by Spahn C. M. (2001)10.1016/0042-6822(81)90004-0
/ Virology by Svitkin Y. V. (1981)10.1126/science.285.5424.107
/ Science by Taylor D. R. (1999)10.1073/pnas.241286698
/ Proc. Natl. Acad. Sci. USA by Thompson S. R. (2001)10.1007/978-3-642-81309-2_1
/ Mol. Biol. Biochem. Biophys by Vazquez D. (1979)10.1101/gad.357006
/ Genes Dev by Ventoso I. (2006)10.1261/rna.5330503
/ RNA by Vyas J. (2003)10.1016/S0092-8674(00)00055-6
/ Cell by Wilson J. E. (2000)10.1073/pnas.90.12.5428
/ Proc. Natl. Acad. Sci. USA by Wong I. (1993)10.1016/S0092-8674(00)80220-2
/ Cell by Yoo C. J. (1997)
Dates
Type | When |
---|---|
Created | 19 years ago (Aug. 23, 2006, 8:59 p.m.) |
Deposited | 4 years ago (July 31, 2021, 12:13 p.m.) |
Indexed | 3 months ago (May 26, 2025, 8:27 a.m.) |
Issued | 18 years, 9 months ago (Nov. 1, 2006) |
Published | 18 years, 9 months ago (Nov. 1, 2006) |
Published Print | 18 years, 9 months ago (Nov. 1, 2006) |
@article{Robert_2006, title={Initiation of Protein Synthesis by Hepatitis C Virus Is Refractory to Reduced eIF2 · GTP · Met-tRNAiMetTernary Complex Availability}, volume={17}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e06-06-0478}, DOI={10.1091/mbc.e06-06-0478}, number={11}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Robert, Francis and Kapp, Lee D. and Khan, Shakila N. and Acker, Michael G. and Kolitz, Sarah and Kazemi, Shirin and Kaufman, Randal J. and Merrick, William C. and Koromilas, Antonis E. and Lorsch, Jon R. and Pelletier, Jerry}, editor={Schmid, Sandra}, year={2006}, month=nov, pages={4632–4644} }