Immune responses play a critical role in fighting tumors and viral infections.An antigenic epitope is a basic unit that elicits either a cellular or a humoral immune response.A multi-epitope vaccine composed of a seri...Immune responses play a critical role in fighting tumors and viral infections.An antigenic epitope is a basic unit that elicits either a cellular or a humoral immune response.A multi-epitope vaccine composed of a series of or overlapping peptides is therefore an ideal approach for the prevention and treatment of tumors or viral infections.1,2,3,4,5 Although some multi-epitope vaccines have entered phase I clinical trials,for example,EMD640744 in patients with advanced solid tumors,6 designing efficacious multi-epitope vaccines remains a great challenge.An ideal multi-epitope vaccine should be designed to include epitopes that can elicit CTL,Th and B cells and induce effective responses against a targeted tumor or virus(Figure 1).展开更多
We have previously reported that bovine papillomavirus type 1(BPV-1) DNA can replicate its genome and produce infectious virus-like particles in short term virion-infected S. cerevisiae(budding yeast) cultures(Zhao an...We have previously reported that bovine papillomavirus type 1(BPV-1) DNA can replicate its genome and produce infectious virus-like particles in short term virion-infected S. cerevisiae(budding yeast) cultures(Zhao and Frazer 2002,Journal of Virology, 76:3359–64 and 76:12265–73). Here, we report the episomal replications of BPV-1 DNA in long term virion-infected S. cerevisiae culture up to 108 days. Episomal replications of the BPV-1 DNA could be divided into three patterns at three stages, early active replication(day 3–16), middle weak replication(day 23–34/45) and late stable replication(day 45–82). Two-dimensional gel electrophoresis analysis and Southern blot hybridization have revealed further that multiple replication intermediates of BPV-1 DNA including linear form, stranded DNA, monomers and higher oligomers were detected in the virion-infected yeast cells over the time course. Higher oligomers shown as covalently closed circular DNAs(cccDNAs) are the most important replication intermediates that serve as the main nuclear transcription template for producing all viral RNAs in the viral life cycle. In this study, the cccDNAs were generated at the early active replication stage with the highest frequencies and then at late stable replication, but they appeared to be suppressed at the middle weak replication. Our data provided a novel insight that BPV-1 genomic DNA could replicate episomally for the long period and produce the key replication intermediates cccDNAs in S. cerevisiae system.展开更多
文摘Immune responses play a critical role in fighting tumors and viral infections.An antigenic epitope is a basic unit that elicits either a cellular or a humoral immune response.A multi-epitope vaccine composed of a series of or overlapping peptides is therefore an ideal approach for the prevention and treatment of tumors or viral infections.1,2,3,4,5 Although some multi-epitope vaccines have entered phase I clinical trials,for example,EMD640744 in patients with advanced solid tumors,6 designing efficacious multi-epitope vaccines remains a great challenge.An ideal multi-epitope vaccine should be designed to include epitopes that can elicit CTL,Th and B cells and induce effective responses against a targeted tumor or virus(Figure 1).
基金This work was funded in part by grants from the National Nature Science Foundation of China(81772791 and 81172463)。
文摘We have previously reported that bovine papillomavirus type 1(BPV-1) DNA can replicate its genome and produce infectious virus-like particles in short term virion-infected S. cerevisiae(budding yeast) cultures(Zhao and Frazer 2002,Journal of Virology, 76:3359–64 and 76:12265–73). Here, we report the episomal replications of BPV-1 DNA in long term virion-infected S. cerevisiae culture up to 108 days. Episomal replications of the BPV-1 DNA could be divided into three patterns at three stages, early active replication(day 3–16), middle weak replication(day 23–34/45) and late stable replication(day 45–82). Two-dimensional gel electrophoresis analysis and Southern blot hybridization have revealed further that multiple replication intermediates of BPV-1 DNA including linear form, stranded DNA, monomers and higher oligomers were detected in the virion-infected yeast cells over the time course. Higher oligomers shown as covalently closed circular DNAs(cccDNAs) are the most important replication intermediates that serve as the main nuclear transcription template for producing all viral RNAs in the viral life cycle. In this study, the cccDNAs were generated at the early active replication stage with the highest frequencies and then at late stable replication, but they appeared to be suppressed at the middle weak replication. Our data provided a novel insight that BPV-1 genomic DNA could replicate episomally for the long period and produce the key replication intermediates cccDNAs in S. cerevisiae system.
