Caspases are not involved in the cleavage of translation initiation factor eIF4GI during picornavirus infection.
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.
Roberts
L O
LO
School of Biological Sciences, University of Surrey, Guildford, Surrey GU2 5XH, UK. l.roberts@surrey.ac.uk
Boxall
A J
AJ
Lewis
L J
LJ
Belsham
G J
GJ
Kass
G E
GE
D000818:Animals; D005537:Aphthovirus / Q000502:physiology*; D017209:Apoptosis; D020169:Caspases / Q000502:physiology*; D006224:Cricetinae; D039603:Eukaryotic Initiation Factor-4G; D006367:HeLa Cells; D006801:Humans; D010448:Peptide Initiation Factors / Q000378:metabolism*; D017955:Poliovirus / Q000502:physiology*
D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors; D020169:Caspases