GENETIC STRUCTURE OF MURINE RETROVIRUSES

该项目的当前目标是确定和描述 生态型小鼠白血病病毒产生的重组体类型 (MuLV)和内源性逆转录病毒基因序列。重组蛋白的分析 小鼠接种不同毒株后产生的多嗜性病毒 生态型MULV证明不同的MULV特定地重组 与特定的内源性逆转录病毒序列一起产生重组子。 来自不同内源序列的多嗜性病毒表现出 不同的生物学特性，包括它们的致癌性及其在 体外寄主范围。后产生的多嗜性病毒分析 体外构建的重组体在生态型MULV间的接种 它们在重组的特异性上存在差异，它们已经鉴定出3‘ 病毒基因组的LTR值作为影响特异性的区域。 AKR/J小鼠携带内源性亲生病毒，发病率较高 自发性淋巴瘤。利用免疫荧光分析 单抗，两种新型的重组病毒已经被 在白血病前期ADR/J小鼠中发现。重组病毒的分离 取自1个月大的小白鼠的脾。这些分离物 具有多嗜性病毒特有的抗原，但表现出更多 在体外寄主范围有限。与多嗜性病毒不同的是，它们 不感染SC-1(小鼠)或水貂肺成纤维细胞，但具有高度传染性 作为小鼠邓尼氏细胞系。在大约4个月大的时候，第二种类型的 在胸腺中检测到重组病毒。SC-1、明克和邓尼家鼠 这些重组子只能通过与 胸腺细胞。这两种类型的重组MuLV是最早的和 在白血病前期小鼠中发现的最常见的重组子及其在 白血病的发生正在调查中。

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.