IMMUNOLOGY OF VIRUS INDUCED PAPILLOMAS/CARCINOMAS

宫颈癌是全世界女性最常见的癌症之一。 大多数，如果不是全部的话，都含有人类乳头瘤病毒(HPV)DNA和HPV 存在的类型是与良性或非良性的HPV类型的子组 癌前生殖器病变。癌症是从癌前病变演变而来的 与癌症相关的亚组的病变。在癌症方面，也在癌症方面 癌症衍生细胞系，病毒DNA继续转录 编码两种早期蛋白质，E6和E7。棉尾兔 乳头瘤病毒(CRPV)及其引起的肿瘤为动物提供了一种 研究宿主、病毒和进化之间相互作用的模型 肿瘤。CRPV诱导角化中的良性肿瘤(乳头状瘤) 家兔和棉尾兔(自然宿主)的上皮组织。 乳头状瘤可自发消退或持续发展为侵袭性 和高频率转移的癌症，特别是在国内 兔子。与人类癌症一样，E6和E7蛋白的mRNA是 在兔癌中含量最高。 我们的长期目标是在广义上阐明各种东道主 兔子系统中的相互作用。具体目标是： 1.免疫状态的特征 A.在乳头状瘤发展过程中。 B.在自发回归过程中。 C.在癌症的发展过程中。 通过；i)血清中非结构病毒抗体的分析 蛋白质。二)检查CRPV特异性细胞毒性T细胞 (CTL)和映射这些细胞识别的病毒表位。Iii) 淋巴增殖性(T细胞)对病毒反应的测定 从病毒或致癌物中提取的多肽或蛋白质(DMBA) 诱导的乳头状瘤或表达病毒蛋白的细胞。四)测量 迟发性超敏反应。 2.关于乳头状瘤和癌细胞的特征 需要表达病毒和辅助蛋白(MHC和ICAM) 用于免疫识别。 3.免疫反应的修饰 A.在挑战病毒或病毒DNA之前 B.在乳头状瘤发展过程中。 C.进展为癌症后。 通过；i)表达重组痘苗病毒的免疫 非结构或结构CRPV蛋白。二)免疫接种 由病毒或DMBA制成的疫苗可诱发肿瘤。Iii) 细胞因子的应用。

Cervical cancer is one of the most common cancers in women world-wide. Most, if not all, contain human papillomavirus (HPV) DNA and the HPV types present are a subgroup of HPV types associated with benign or premalignant genital lesions. The cancers evolve from premalignant lesions of the cancer associated subgroup. In cancer, as well as in cancer derived cell lines, viral DNA continues to be transcribed which encodes the two early proteins, E6 and E7. The cottontail rabbit papillomavirus (CRPV) and the neoplasias induced by it provide an animal model to study the interactions between host, virus and the evolving neoplasias. CRPV induces benign tumors (papillomas) in the keratinizing epithelium of domestic and cottontail rabbits (the natural host). Papillomas may regress spontaneously or persist and progress to invasive and metastasizing cancers at a high frequency, particularly, in domestic rabbits. As in the human cancers, mRNA for the E6 and E7 proteins are the most abundant in rabbit cancers. Our long-term goal is to elucidate in a broad sense various host interaction in the rabbit system. The specific aims are: 1. Characterization of the immune status a. During papilloma development. b. During spontaneous regression. c. During development of cancers. By; i) The analysis of serum for antibodies to nonstructural viral proteins. ii) Checking for CRPV specific cytotoxic T cell lymphocytes (CTL) and mapping viral epitopes recognized by these cells. iii) Determination of the lymphoproliferative (T cell) response to viral peptides or proteins, to extracts from virus or carcinogen (DMBA) induced papillomas or to cells expressing viral proteins. iv) Measuring delayed type hypersensitivity. 2. Characterization of papilloma and carcinoma cells with respect to the expression of viral and auxiliary proteins (MHC and ICAM) required for immune recognition. 3. Modification of the immune response a. Before challenge with virus or viral DNA b. During papilloma development. c. After progression to carcinomas. By; i) Immunization with recombinant vaccinia virus expressing nonstructural or structural CRPV proteins. ii) Immunization with vaccines prepared from virus or DMBA induced tumors. iii) Administration of cytokines.