VIRAL DETERMINANTS OF PATHOGENESIS BY FELVS AND HTLV-I

逆转录病毒既能引起消融，也能引起增殖。 淋巴网状系统疾病。T细胞的诱导 猫的白血病/淋巴瘤与A亚群和亚群感染有关 B猫白血病病毒(FeLV)，以及感染I型的人 人T细胞淋巴病毒(HTLV-I)。相比之下，C亚组FELV 会导致猫再生障碍性贫血，而HTLV-III可能是导致 人类中的艾滋病。因为由FeLV和HTLV引起的疾病谱 如此相似，FeLV被认为是最合适的动物模型 与病毒相关的人类恶性肿瘤和艾滋病。我建议分子和 猪瘟病毒A、B、C和HTLV-I原型病毒的生物学分析 定义它们生物活性的关键方面和基因 决定这些属性的功能。分子研究将包括 天然产物的转录分析、分子克隆和DNA测序 病毒分离及重组FeLV和FeLV/HTLV的产生 克隆DNA的体外操作。生物学研究将包括 转染法和转录活性检测、病毒生产和 幼鼠胚胎转化过程中对癌基因的补体能力 成纤维细胞。通过转基因获得的某些病毒也将被 接种家猫以监测致病活动。

Retroviruses are capable of inducing ablative as well as proliferative diseases of the lymphoreticular system. Induction of T-cell leukemia/lymphoma is associated in cats with infection with subgroups A and B Feline Leukemia Viruses (FeLV), and in humans with infection with Type I Human T-cell Lymphotrophic Viruses (HTLV-I). In contrast, subgroup C FeLVs will induce aplastic anemia in cats, and HTLV-III is the probable cause of AIDS in humans. Because the spectrum of disease induced by FeLV and HTLV is so similar, FeLV is considered to be the most appropriate animal model for virus-associated human malignancy and AIDS. I propose molecular and biological analyses of FeLV A, B and C and HTLV-I prototype viruses to define crucial aspects of their biological activity and the genetic features which determine these properties. Molecular studies will include transcription analysis, molecular cloning and DNA sequencing of natural virus isolates and generation of recombinent FeLV and FeLV/HTLV following in-vitro manipulation of cloned DNAs. Biological studies will include transfection and tests for transcriptional activity, virus production and ability to complement oncogenes in transformation of naive rat embryo fibroblasts. Certain viruses derived by transfection will also be inoculated into domestic cats to monitor pathogenic activity.