Development of Fungal and Algal Cells for Expression of Herpes Virus Genes

Abstract

The advances of recombinant DNA technology have permitted the routine isolation and characterization of genes of medical and virologic interests. Most of these genes can be re-expressed into functional proteins upon reintroduction into suitable host cells. It is by now quite apparent that the expression of a gene into functional protein depends not only on the nature of the expressed protein, but on the post-translation modifications available in the host cells as well. For example, the expression and assembly of hepatitis B virus surface antigen (HB_sAg) polypeptide into the antigenic and immunogenic 22-nm particle was readily carried out in yeast cells (Valenzuela et al., 1982), but not in Escherichia coli. The recent demonstration that chymosin can be expressed and secreted in functional form in the filamentous fungus Aspergillus, but not in E. coli, serves as another example. More subtle and intricate differences do exist even in closely related host cells. For example, the human growth hormone expressed in E. coli retained the N-terminal methionine, while the same polypeptide expressed in Pseudomonas was properly processed and even secreted (Gregory et al., 1984). The mammalian cells and insect cells have now been used quite frequently for the expression of human and viral genes, which require glycosylation and protein processing to produce functional gene products. However, they are by no means host cells of universal applicability. There are instances in which genes failed to express, or expressed only in minute amounts (e.g., blood coagulation factor VIII gene), when they were reintroduced back into mammalian cells (Wood et al., 1984).