Study of a DNA vaccine of the papillomavirus

在以前的研究中，我们开发了一个高度可重复的致癌模型相结合的DMBA应用与仓鼠舌粘膜的物理创伤。组织学上，这些病变表现出指示乳头瘤病毒感染的病理特征性变化，如发育不良细胞的挖空细胞，并且一些发育不良或癌细胞的细胞核对乳头瘤病毒属特异性抗原（GSA）呈阳性。此外，在这些细胞的细胞核中检测到直径为50-55 nm的类似乳头瘤病毒的病毒颗粒。使用这种动物模型，我们证明了一种新的仓鼠乳头状瘤病毒的存在，通过分子克隆和测序这种病毒基因组。经全序列分析证实，该病毒为一种新型乳头瘤病毒，命名为仓鼠口腔乳头瘤病毒（HOPV）。此外，我们还用原位杂交技术在金黄地鼠舌上皮的不典型增生和恶性病变的细胞核中检测到HOPV。Co 关于我们 计算机辅助系统发育分析表明，HOPV与其他乳头瘤病毒在基因组的不同区域具有不同的同源性。该病毒基因组全长7647 bp，G+C含量为46.6%。该大小与MnPV（7687 bp）的大小相似。该基因组在一条链上具有开放阅读框（ORF），显示通常的顺序：ORF E6、E7、E1、E2、L2和L1。ORF E2包含小ORF E4。ORF H5缺失。这些克隆的基因组不同于其他啮齿动物乳头瘤病毒，如MmPV和MnPV，也不同于以前测序的动物和人乳头瘤病毒基因组。仓鼠肌肉注射HOPV E6/E7/L1质粒DNA两次，间隔3周。用这些裸pDNAs观察保护作用。因此，HOPV感染似乎是研究与乳头瘤病毒相关的粘膜癌发生以及研究疫苗预防和预防或治疗恶性转化的良好模型。少

In a previous investigation, we developed a highly reproducible carcinogenesis model by combining DMBA application with physical wounding of the hamster lingual mucosa. Histologically, these lesions showed pathognomonic changes indicative of papillomavirus infection, such as koilocytosis of dysplastic cells, and the nuclei of some dysplastic or cancerous cells were positive for papillomavirus genus-specific antigen (GSA). Furthermore, viral particles resembling papillomavirus, whose size was 50-55 nm in diameter, have been detected in the nuclei of these cells. Using this animal model, we demonstrated the presence of a novel hamster papillomavirus by the molecular cloning and sequencing of this viral genome. The genome was confirmed by complete sequence analysis to be a novel papillomavirus which we designated the hamster oral papillomavirus (HOPV). Moreover, we detected HOPV in the nuclei of dysplastic and malignant lesions in hamster lingual epithelium using in situ hybridization. Co … More mputer-assisted phylogenetic analysis of HOPV showed a differing homology with other papillomaviruses in different regions of the genomes. The complete nucleotide sequence of this viral genome consists of 7647bp with a G+C content of 46.6%. This size is similar to that of MnPV(7687bp). This genome has open reading frames (ORFs) on one strand showing the usual order : ORFs E6, E7, E1, E2, L2 and L1. ORF E2 contains the small ORF E4. ORF H5 is missing. These cloned genomes are different from those of other rodent papillomaviruses, such as MmPV and MnPV, and also from previously sequenced animal and human papillomavirus genomes.We evaluated a prophylactic effect of DNA vaccination. Hamsters were injected intramusccularly with HOPV E6/E7/L1 plasmid DNA two times at 3-week intervals. The protective effect was observed with those naked pDNAs. Therefore, HOPV infection seems to be a good model for the study on mucosal carcinogenesis associated with papillomavirus and for studies on vaccine prophylaxis and the prevention or treatment of malignant conversion. Less