Inhibition of coronavirus MHV-A59 replication by proteinase inhibitors.

Replication of mouse hepatitis virus is initiated by translation and processing of the gene 1 polyprotein. The increasing complexity of this pattern of replicase protein expression is becoming apparent. MHV-A59 encodes approximately 800 kDa of polypeptide within the two overlapping open reading frames of gene 1. In addition, at least one proteinase activity encoded by gene 1 has been identified1,2 and two more are predicted, along with putative polymerase, helicase, NTP binding and possibly growth factor like proteins3–5. Only the first 380 kDa of protein products of MHV gene 1 ORF 1a have been described and characterized as to the pattern of expression and processing in virus infected cells6. Specifically, proteins of N-p28-65-290-C constitute the initial translation products of this region. The cleavage between p28 and p65 has been best described, both in vitro and in virus-infected cells7. As of yet no specific functions have been ascribed to any of these proteins. Thus a great deal remains to be learned about the processing pattern and functions of MHV gene 1 encoded proteins.