PATHOGENETIC MECHANISMS IN FELINE LEUKEMIA

该计划的长期目标是确定多个事件 国内淋巴恶性肿瘤发病机制中的相互作用 猫。该近交物种的白血病-淋巴瘤发病率最高 任何动物的感染，以及自然发生的猫科动物的水平感染 白血病病毒（FeLV）是导致其易感性增加的原因 白血病发生。对于所发生的事件还有很多事情有待发现 在长时间的病毒血症期间。目前的证据表明 传染性 FeLV 与非传染性 FeLV 之间的重组事件 内源性遗传的 FeLV 样元件，可产生高致病性 变异病毒。重组病毒表面很可能 糖蛋白通过以下方式提供对预期靶细胞的识别 该病毒也可能以相同或变异的形式对人体产生独立的影响 细胞增殖/胚细胞发生和细胞病变。其他因素 导致肿瘤疾病的因素包括插入激活的 细胞基因如 c-myc 和 flvi-2 以及增加的增益 通过病毒突变增强转录活性 转录调控元件。 FeLV-中的免疫活性受损 受感染的猫也会对肿瘤的发展产生影响。 建议继续进行分子认识的研究 决定靶细胞趋向性、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 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。实验的目的是检验潜力 嵌合病毒糖蛋白通过直接或 间接影响细胞增殖、分化或凋亡。 此外，适当的猫科淋巴肉瘤标本代表 大多数未表征的原病毒插入位点已被识别并 选择，对其分析应该为 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起来应该会产生新的见解 近交系中逆转录病毒诱导的淋巴癌的发病机制 动物种类。

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.