Many picornaviruses cause a dramatic decrease in the translation of cellular mRNAs in the infected cell, without affecting the translation of their own
RNA. Specific proteolysis of
protein synthesis
initiation factor eIF-4 gamma occurs during
infection with rhinoviruses, enteroviruses, and aphthoviruses, apparently leading to an inability of the ribosomes to bind capped mRNAs. Cleavage of
eIF-4 gamma in human rhinoviruses and enteroviruses is carried out by the viral 2A
proteinase; in aphthoviruses (i.e., foot-and-mouth disease viruses), the leader
proteinase is responsible for this reaction. We describe here the purification to homogeneity of the Lb form of the leader
proteinase expressed in Escherichia coli. The primary cleavage products of
eIF-4 gamma obtained in vitro with purified leader or 2A
proteinase are electrophoretically indistinguishable from those found during
infection in vivo. However, additional proteolysis products of
eIF-4 gamma are observed with the leader
proteinase and the human rhinovirus type 2 2A
proteinase in vitro. The cleavage site of the leader
proteinase in eIF-4 gamma from rabbit reticulocyte was determined by sequencing the purified C-terminal cleavage product by automated Edman degradation. The cleavage site is between Gly-479 and Arg-480 and thus differs from that of rhinovirus and enterovirus 2A
proteinases, which cleave between Arg-486 and Gly-487.