Downstream Sequences Control the Processing of the Pestivirus E rns -E1 Precursor

Abstract

Cellular signal peptidase (SPase) cleavage represents an important step in maturation of viral envelope proteins. Fine tuning of this system allows for establishment of concerted folding and processing processes in different enveloped viruses. We report here on SPase processing of the E rns -E1-E2 glycoprotein precursor of pestiviruses. E rns -E1 cleavage is delayed and only executed efficiently when the complete E1 sequence is present. C-terminal truncation of the E rns -E1 precursor impairs processing and leads to significant secretion of the protein. The latter is not detected when internal deletions preserving the E1 carboxy terminus are introduced, but also these constructs show impaired processing. Moreover, E rns -E1 is only processed after cleavage at the E1/E2 site. Thus, processing of the pestiviral glycoprotein precursor by SPase is done in an ordered way and depends on the integrity of the proteins for efficient cleavage. The functional importance of this processing scheme is discussed in the paper.