Infection of cells by many picornaviruses results in the rapid inhibition of cellular protein synthesis due to cleavage of the translation initiation factor eIF4G. The poliovirus (PV) 2A and foot-and-mouth disease virus (FMDV) L proteases are each sufficient to mediate this cleavage, but the cleavage mechanism may be indirect, involving an unidentified cellular protease(s). eIF4G is also targetted for cleavage by caspase-3 during apoptosis. Here, it is shown that caspase inhibitors do not inhibit the cleavage of eIF4GI during PV or FMDV infection. Similarly, in transient-expression studies, the cleavage of eIF4GI induced by PV 2A or FMDV L was unaffected by these inhibitors. Furthermore, the cleavage of eIF4GI was observed in PV-infected MCF-7 cells lacking caspase-3. These data, and the fact that induction of apoptosis yields different eIF4GI cleavage fragments, indicate that caspases do not have a major role in the cleavage of eIF4GI during PV or FMDV infection.
Agol, V. I., Belov, G. A., Bienz, K., Egger, D., Kolesnikova, M. S., Raikhlin, N. T., Romanova, L. I., Smirnova, E. A. & Tolskaya, E. A. (1998). Two types of death of poliovirus-infected cells: caspase involvement in the apoptosis but not cytopathic effect. Virology252, 343-353.[CrossRef][Google Scholar]
Ashkenazi, A. & Dixit, V. M. (1999). Apoptosis control by death and decoy receptors. Current Opinion in Cell Biology11, 255-260.[CrossRef][Google Scholar]
Belsham, G. J. & Sonenberg, N. (1996). RNA–protein interactions in regulation of picornavirus RNA translation. Microbiological Reviews60, 499-511.
[Google Scholar]
Belsham, G. J., McInerney, G. M. & Ross-Smith, N. (2000). Foot-and-mouth disease virus 3C protease induces cleavage of translation initiation factors eIF4A and eIF4G within infected cells. Journal of Virology74, 272-280.[CrossRef][Google Scholar]
Bonneau, A.-M. & Sonenberg, N. (1987). Proteolysis of the p220 component of the cap-binding protein complex is not sufficient for complete inhibition of host cell protein synthesis after poliovirus infection. Journal of Virology61, 986-991.
[Google Scholar]
Borman, A. M., Kirchweger, R., Ziegler, E., Rhoads, R. E., Skern, T. & Kean, K. M. (1997). eIF4G and its proteolytic cleavage products: effect on initiation of protein synthesis from capped, uncapped, and IRES-containing mRNAs. RNA3, 186-196.
[Google Scholar]
Bovee, M. L., Marissen, W. E., Zamora, M. & Lloyd, R. E. (1998a). The predominant eIF4G-specific cleavage activity in poliovirus-infected HeLa cells is distinct from 2A protease. Virology245, 229-240.[CrossRef][Google Scholar]
Bovee, M. L., Lamphear, B. J., Rhoads, R. E. & Lloyd, R. E. (1998b). Direct cleavage of eIF4G by poliovirus 2A protease is inefficient in vitro. Virology245, 241-249.[CrossRef][Google Scholar]
Bushell, M., McKendrick, L., Janicke, R. U., Clemens, M. J. & Morley, S. J. (1999). Caspase-3 is necessary and sufficient for cleavage of protein synthesis eukaryotic initiation factor 4G during apoptosis. FEBS Letters451, 332-336.[CrossRef][Google Scholar]
Carthy, C. M., Granville, D. J., Watson, K. A., Anderson, D. R., Wilson, J. E., Yang, D. C., Hunt, D. W. C. & McManus, B. M. (1998). Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells. Journal of Virology72, 7669-7675.
[Google Scholar]
Chow, S. C., Weis, M., Kass, G. E. N., Holmström, T. H., Eriksson, J. E. & Orrenius, S. (1995). Involvement of multiple proteases during Fas-mediated apoptosis in T lymphocytes. FEBS Letters364, 134-138.[CrossRef][Google Scholar]
Clemens, M. J., Bushell, M. & Morley, S. J. (1998). Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines. Oncogene17, 2921-2931.[CrossRef][Google Scholar]
Devaney, M. A., Vakharia, V. N., Lloyd, R. E., Ehrenfeld, E. & Grubman, M. J. (1988). Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex. Journal of Virology62, 4407-4409.
[Google Scholar]
Etchison, D. & Fout, S. (1985). Human rhinovirus 14 infection of HeLa cells results in the proteolytic cleavage of the p220 cap-binding complex subunit and inactivates globin mRNA translation in vitro. Journal of Virology54, 634-638.
[Google Scholar]
Etchison, D., Milburn, S., Edery, I., Sonenberg, N. & Hershey, J. W. B. (1982). Inhibition of HeLa cell protein synthesis following picornavirus infection correlates with the proteolysis of a 220,000 dalton polypeptide associated with eukaryotic initiation factor 3 and a cap-binding complex. Journal of Biological Chemistry257, 14806-14810.
[Google Scholar]
Fuerst, T. R., Niles, E. G., Studier, F. W. & Moss, B. (1986). Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proceedings of the National Academy of Sciences, USA83, 8122-8126.[CrossRef][Google Scholar]
Gradi, A., Imataka, H., Svitkin, Y. V., Rom, E., Raught, B., Morino, S. & Sonenberg, N. (1998). A novel functional human eukaryotic translation initiation factor 4G. Molecular Cell Biology18, 334-342.
[Google Scholar]
Green, D. R. & Reed, J. C. (1998). Mitochondria and apoptosis. Science281, 1309-1312.[CrossRef][Google Scholar]
Haghighat, A. & Sonenberg, N. (1997). eIF4G dramatically enhances the binding of eIF4E to the mRNA 5′-cap structure. Journal of Biological Chemistry272, 21677-21680.[CrossRef][Google Scholar]
Imataka, H., Gradi, A. & Sonenberg, N. (1998). A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation. EMBO Journal17, 7480-7489.[CrossRef][Google Scholar]
Jackson, R. J., Hunt, S. L., Gibbs, C. L. & Kaminski, A. (1994). Internal initiation of translation of picornavirus RNAs. Molecular Biology Reports19, 147-159.[CrossRef][Google Scholar]
Jänicke, R. U., Sprengart, M. L., Wati, M. R. & Porter, A. G. (1998). Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. Journal of Biological Chemistry273, 9357-9360.[CrossRef][Google Scholar]
Jones, R. A., Johnson, V. L., Buck, N. R., Dobrota, M., Hinton, R. H., Chow, S. C. & Kass, G. E. N. (1998). Fas-mediated apoptosis in mouse hepatocytes involves the processing and activation of caspases. Hepatology27, 1632-1642.[CrossRef][Google Scholar]
Kaminski, A., Howell, M. T. & Jackson, R. J. (1990). Initiation of encephalomyocarditis virus RNA translation: the authentic initiation site is not selected by a scanning mechanism. EMBO Journal9, 3753-3759.
[Google Scholar]
Kirchweger, R., Ziegler, E., Lamphear, B. J., Waters, D., Liebig, H. D., Sommergruber, W., Sobrino, F., Hohenadl, C., Blaas, D., Rhoads, R. E. & Skern, T. (1994). Foot-and-mouth disease virus leader proteinase: purification of the Lb form and determination of its cleavage site on eIF-4 gamma. Journal of Virology68, 5677-5684.
[Google Scholar]
Kräusslich, H.-G., Nicklin, M. J. H., Toyoda, H., Etchison, D. & Wimmer, E. (1987). Poliovirus proteinase 2A induces cleavage of eucaryotic initiation factor 4F polypeptide p220. Journal of Virology61, 2711-2718.
[Google Scholar]
Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227, 680-685.[CrossRef][Google Scholar]
Lamphear, B. J., Kirchweger, R., Skern, T. & Rhoads, R. E. (1995). Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. Journal of Biological Chemistry270, 21975-21983.[CrossRef][Google Scholar]
Lloyd, R. E., Toyoda, H., Etchison, D., Wimmer, E. & Ehrenfeld, E. (1986). Cleavage of the cap binding protein complex p220 is not effected by the second poliovirus protease 2A. Virology150, 229-303.
[Google Scholar]
Lloyd, R. E., Grubman, M. J. & Ehrenfeld, E. (1988). Relationship of p220 cleavage during picornavirus infection to 2A proteinase sequences. Journal of Virology62, 4216-4223.
[Google Scholar]
MacFarlane, M., Ahmad, M., Srinivasula, S. M., Fernandes-Alnemri, T., Cohen, G. M. & Alnemri, E. S. (1997). Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. Journal of Biological Chemistry272, 25417-25420.[CrossRef][Google Scholar]
Marissen, W. E. & Lloyd, R. E. (1998). Eukaryotic translation initiation factor 4G is targeted for proteolytic cleavage by caspase 3 during inhibition of translation in apoptotic cells. Molecular Cell Biology18, 7565-7574.
[Google Scholar]
Medina, M., Domingo, E., Brangwyn, J. K. & Belsham, G. J. (1993). The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology194, 355-359.[CrossRef][Google Scholar]
Morley, S. J., McKendrick, L. & Bushell, M. (1998). Cleavage of translation initiation factor 4G (eIF4G) during anti-Fas IgM-induced apoptosis does not require signalling through the p38 mitogen-activated protein (MAP) kinase. FEBS Letters438, 41-48.[CrossRef][Google Scholar]
Ohlmann, T., Rau, M., Pain, V. M. & Morley, S. J. (1996). The C-terminal domain of eukaryotic protein synthesis initiation factor (eIF) 4G is sufficient to support cap-independent translation in the absence of eIF4E. EMBO Journal15, 1371-1382.
[Google Scholar]
Roberts, L. O., Seamons, R. A. & Belsham, G. J. (1998). Recognition of picornavirus internal ribosome entry sites within cells; influence of cellular and viral proteins. RNA4, 520-529.[CrossRef][Google Scholar]
Ryan, M. D. & Flint, M. (1997). Virus-encoded proteinases of the picornavirus super-group. Journal of General Virology78, 699-723.
[Google Scholar]