MENGOVIRUS LEADER IS INVOLVED IN THE INHIBITION OF HOST-CELL PROTEIN-SYNTHESIS

The presence of a leader peptide in picornaviruses is restricted to th e Cardiovirus and Aphthovirus genera, However, the leader peptides of these two genera are structurally and functionally unrelated, The apht hovirus leader is a protease involved in viral polyprotein processing and host cell translation shutoff. The function of the cardiovirus lea der peptide is still unknown, To gain an insight into the function of the cardiovirus leader peptide, a mengovirus leader peptide deletion m utant was constructed, The deletion mutant was able to grow at a reduc ed rate in baby hamster kidney cells (BHK-21), Mutant virus production in mouse fibroblasts (L929 cells), however, could be demonstrated onl y after inoculation of BHK-21 cells with the transfected L929 cells, A nalysis of cellular and viral protein synthesis in mutant virus-infect ed cells showed a delayed inhibition of host cell protein synthesis an d a reduced production of viral proteins, In a single-cycle infection, mutant virus produced only 1% of wild-type virus yield at 8 h postinf ection, Host cell translation shutoff in L929 cells infected with muta nt virus was restored by the addition of the kinase inhibitor 2-aminop urine. Mutant virus production in 2-aminopurine-treated L929 cells was increased to 60% of wild-type virus yield at 8 h postinfection. Our r esults suggest that the cardiovirus leader peptide is involved in the inhibition of host cell protein synthesis.