EXPRESSION OF THE MAJOR CAPSID PROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-11 IN SACCHAROMYCES-CEREVISAE

The major capsid protein L1 of papillomaviruses expressed recombinantl y or in infected cells has the intrinsic ability to form virus-like pa rticles (VLPs) which display conformational epitopes necessary to elic it high-titered, virus-neutralizing antibodies. We have shown previous ly that the L1 gene of human papillomavirus type 6a (HPV6) can be expr essed efficiently in Saccharomyces cerevisae (Sc) as VLPs. However, wh en we attempted to express the L1 gene cloned from the closely related HPV11 in yeast, few VLPs were observed in crude lysates. The lower ex pression level of HPV11 L1 protein was found to result from a truncati on of the HPV11 L1 mRNA. Since sequence requirements for transcription al termination in yeast are still unclear, the HPV6 L1 gene was used a s the basis for the complete synthetic reconstruction of the entire 15 06-bp HPV11 L1 gene. Expression of this HPV6/11 hybrid L1 gene in yeas t resulted in predominantly full-length L1 mRNA and a >7-fold increase d level of production of HPV11 VLPs compared to that expressed by the wild-type HPV11 L1 gene. The VLPs were shown to display the conformati onal epitopes important to elicit virus-neutralizing antibodies.