PATHOGENETIC MECHANISMS IN FELINE LEUKEMIA

猫白血病的致病机制

• 批准号: 2871744
• 负责人: PRADIP ROY-BURMAN
• 金额: $ 33.33万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2871744
• 关键词: apoptosis; cats; feline leukemia /sarcoma virus; genetic recombination; host organism interaction; immunofluorescence technique; immunosuppression; lymphosarcoma; molecular cloning; newborn animals; polymerase chain reaction; protooncogene; viral carcinogenesis; viral leukemia; virus envelope; virus genetics

The long-term goal of this program is to identify the multiple events that interplay in the pathogenesis of lymphoid malignancies in the domestic cat. This outbred species has the highest incidence of leukemia-lymphoma of any animal, and horizontal infection of the naturally occurring feline leukemia virus (FeLV) is responsible for its increased susceptibility to leukemogenesis. Much remains to be discovered for the events that occur during the prolonged viremic period. Current evidence suggests recombinational events between the infectious FeLV and non-infectious endogenously inherited FeLV-like elements which generate highly pathogenic variant viruses. It is likely that the recombinant viral surface glycoproteins which provide recognition of the prospective target cell by the virus may also have independent effect in the same or variant forms on cell proliferation/blastogenesis and cytopathicity. Other factors that contribute to neoplastic disease include the insertionally activated cellular genes such as c-myc and flvi-2 and the gaining of increased strength in transcriptional activity through mutations in viral transcription regulatory elements. Impaired immunologic activity in FeLV- infected cats also has consequences in tumor development. It is proposed to continue the studies on the molecular understanding of the recombinational parameters that dictate target cell tropism, disease specificity, and immunosuppressive properties. Individual recombinant viruses will be molecularly cloned from pathogenic virus mixtures and from selected naturally occurring lymphosarcomas for the scrutiny of their genetic structure, and in vitro and in vivo biological and pathological properties. Experiments have been designed to examine the potential that chimeric viral glycoproteins contribute to pathogenesis by directly or indirectly influencing cell proliferation, differentiation or apoptosis. In addition, appropriate feline lymphosarcoma specimens representing mostly uncharacterized provirus insertion sites have been identified and selected, analysis of which should provide clues to novel genes in FeLV- induced neoplastic disease. These interconnected studies, in combination, should lead to new insights into the pathogenesis of retrovirus-induced lymphoid cancer in an outbred animal species.

该计划的长期目标是确定符合以下条件的多个事件 国内淋巴系统恶性肿瘤发病机制的相互作用 猫。这种近亲繁殖物种的白血病-淋巴瘤发病率最高。 任何动物的水平感染和自然发生的猫的水平感染 白血病病毒(FeLV)是导致其对 白血病的发生。对于发生的事件，还有很多有待发现的地方 在延长的病毒期内。目前的证据表明 传染性乙型肝炎病毒与非传染性乙型肝炎病毒之间的重组事件 内源性遗传的FeLV样元件，产生高致病性 变种病毒。很可能重组病毒表面 通过以下途径识别预期靶细胞的糖蛋白 病毒也可能以相同或不同的形式对 细胞增殖/母细胞生成和细胞病变。其他因素 导致肿瘤疾病的因素包括插入激活 C-myc和flvi-2等细胞基因与增殖性 通过病毒突变增强转录活性 转录调控元件。FeLV免疫活性受损- 被感染的猫也会导致肿瘤的发展。 建议继续开展分子理解方面的研究。 决定靶细胞嗜性、疾病的重组参数 特异性和免疫抑制特性。个体重组 病毒将从致病病毒混合物中分子克隆，并从 选择自然发生的淋巴肉瘤进行检查 遗传结构、体外和体内生物学和病理学 属性。已经设计了一些实验，以检验 嵌合病毒糖蛋白通过直接或间接参与致病 间接影响细胞的增殖、分化或凋亡。 此外，适当的猫淋巴肉瘤标本代表 已经确定了大多数未表征的前病毒插入位点， 对这些基因的分析将为FeLV中的新基因提供线索- 诱发肿瘤性疾病。 这些相互关联的研究结合在一起，应该会带来新的见解 逆转录病毒诱导的近交系淋巴样癌发病机制的探讨 动物物种。