Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex.
Suppression of host protein synthesis in cells infected by poliovirus and certain other picornaviruses involves inactivation of the cap-binding protein complex. Inactivation of this complex has been correlated with the proteolytic cleavage of p220, a component of the cap-binding protein complex. Since picornaviral RNA is not capped, it continues to be translated as the cap-binding protein complex is inactivated. The cleavage of p220 can be induced to occur in vitro, catalyzed by extracts from infected cells or by reticulocyte lysates translating viral RNA. Expression of polioviral protease 2A is sufficient to induce p220 cleavage, and the presence in 2A of an 18-amino-acid sequence representing a putative cysteine protease active site correlates with the ability of different picornaviruses to induce p220 cleavage. Foot-and-mouth disease virus (FMDV) infection induces complete cleavage of p220, yet the FMDV genome codes for a 2A protein of only 16 amino acids, which does not include the putative cysteine protease active site. Using cDNA plasmids encoding various regions of the FMDV genome, we have determined that the leader protein is required to initiate p220 cleavage. This is the first report of a function for the leader protein, other than that of autocatalytic cleavage from the FMDV polyprotein.
Devaney
M A
MA
U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, New York 11944.
Vakharia
V N
VN
Lloyd
R E
RE
Ehrenfeld
E
E
Grubman
M J
MJ
D005537:Aphthovirus / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D010957:Plasmids; D021382:Protein Sorting Signals / Q000502:physiology*; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps / Q000378:metabolism*; D014764:Viral Proteins / Q000502:physiology
D002352:Carrier Proteins; D021382:Protein Sorting Signals; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps; D014764:Viral Proteins; C057421:virus protein 2A