GENETIC STRUCTURE OF MURINE RETROVIRUSES

鼠逆转录病毒的遗传结构

• 批准号: 4688430
• 负责人: L H EVANS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4688430
• 关键词: genetic recombination; genetic strain; monoclonal antibody; mouse leukemia; murine leukemia virus; mutant; oncogenic virus; provirus; tissue /cell culture; virus antigen; virus classification; virus cytopathogenic effect; virus genetics; virus replication

The current objectives of this project are to identify and characterize the types of recombinants generated between ecotropic murine leukemia virus (MuLVs) and endogenous retroviral gene sequences. Analyses of recombinant polytropic viruses generated after inoculation of mice with different ecotropic MuLVs demonstrated that different MuLVs specifically recombine with particular endogenous retroviral sequences to generate recombinants. Polytropic viruses derived from different endogenous sequences exhibited different biological properties, including their oncogenicity and their in vitro host ranges. Analyses of polytropic viruses generated after inoculation of in vitro-constructed recombinants between ecotropic MuLVs which differ in their specificity of recombination have identified the 3' LTR of the viral genome as a region which influences the specificity. AKR/J mice harbor endogenous ecotropic viruses and exhibit a high incidence of spontaneous lymphomas. Utilizing an immunofluorescence assay with monoclonal antibodies, two novel types of recombinant viruses have been identified in preleukemic ADR/J mice. Recombinant viruses were isolated from the spleens of mice as young as 1 month of age. These isolates possess antigens characteristic of polytropic viruses but exhibit a more limited in vitro host range. In contrast to polytropic viruses, they do not infect SC-1 (mouse) or mink lung fibroblasts, but are highly infectious for a Mus dunni cell line. At about 4 months of age, a second type of recombinant virus was identified in the thymuses. SC-1, mink and Mus dunni cells could only be infected with these recombinants by co-cultivation with thymocytes. These two types of recombinant MuLVs are the earliest and the most prevalent recombinants found in preleukemic mice and their role in leukemogenesis is under investigation.

该项目目前的目标是确定和描述 嗜亲性小鼠白血病病毒之间产生的重组体类型 （MuLV）和内源性逆转录病毒基因序列。 重组分析 用不同的病毒接种小鼠后产生的嗜多性病毒 亲嗜性MuLV表明，不同的MuLV特异性重组， 用特定的内源性逆转录病毒序列产生重组体。 来源于不同内源性序列的多嗜性病毒表现出 不同的生物学特性，包括它们的致癌性和它们的生物学特性， 体外宿主范围。 分析在以下条件下产生的嗜多性病毒 在亲嗜性MuLV之间接种体外构建的重组体 它们在重组的特异性上不同， 病毒基因组的LTR作为影响特异性的区域。 AKR/J小鼠携带内源性嗜亲性病毒， 自发性淋巴瘤 利用免疫荧光测定， 单克隆抗体，两种新型的重组病毒已被 在白血病前ADR/J小鼠中鉴定。 分离重组病毒 从一个月大的小鼠脾脏中提取。 这些分离株 具有多变性病毒的抗原特征，但表现出更多的 体外宿主范围有限。 与多变性病毒相反， 不感染SC-1（小鼠）或貂肺成纤维细胞，但具有高度感染性 老鼠细胞系 在大约4个月大的时候，第二种类型的 在胸腺中鉴定出重组病毒。 SC-1，水貂和Mus dunni 细胞只能通过与以下物质共培养而被这些重组体感染： 胸腺细胞 这两种类型的重组MuLV是最早的， 在白血病前期小鼠中发现的最普遍的重组体及其在 白血病发生正在研究中。