Modified Bovine Herpesvirus 1 for Protein Secretion

Summary

The traditional way to utilize bovine herpesvirus 1 (BHV-1) and many other herpesviruses as vectors for synthesis of heterologous proteins like reporter proteins, antigens, or immunomodulatory active molecules was (and still is) the expression of the protein of interest from an entire gene consisting of promoter, 5′- and 3′-noncoding regions, the open reading frame (ORF), and a signal sequence for polyadenylation. This approach is doubtlessly appropriate especially in cases when expression of large proteins or of proteins that do not enter the secretory pathway is envisaged. My laboratory has developed an alternative expression strategy for secreted proteins and peptides that uses the essential BHV-1 glycoprotein B (gB) as transporter for a cargo protein that is embedded in gB as a furin-excisable polypeptide that is released from the gB precursor molecule in the trans-Golgi network by the ubiquitously present endoprotease furin. The general applicability of this novel expression strategy is demonstrated by using GFP as reporter protein to monitor secretion. We hypothesize that also other secreted or membrane-bound (glyco)proteins can be engineered to function as transporters for oligopeptides and also more complex larger proteins.