NOVEL HUMAN ENDOGENOUS RETROVIRUSES

在这项拨款申请中建议的研究举例说明 继续和扩大我们正在进行的隔离工作， 内源蛋白新家族的鉴定和表达 逆转录病毒。为此，我们计划分离并鉴定一种 据称是一类新的人类内源性逆转录病毒 已经用禽类逆转录病毒特异性遗传探针鉴定出 我们以前曾用来识别新的鸟类类别 内源性逆转录病毒。我们建议的研究包括：(1) 禽类逆转录病毒相关人内源性病毒的分离 家族的分子克隆和核苷酸鉴定 序列分析；(2)表征的程度和性质 这个额外的人类内源性家族的表达 人类正常和恶性细胞类型中的逆转录病毒；以及(3) 这一新的内源性逆转录病毒家族与 其他先前发现的人类内源性基因家族 由不同种类的病毒产生的带有“C”型病毒粒子的逆转录病毒 人类肿瘤包括睾丸生殖细胞肿瘤和 胚胎癌细胞群体分化为 确定这些细菌产生的“C”型粒子 细胞瘤表现出与任何家族的任何序列同源性 人类内源性病毒。我们计划采用的方法 在很大程度上，实现这些目标的员工已经 在我们的实验室中实施，包括各种 物化、酶学和杂交技术 可用于DNA、RNA和蛋白质的分析，包括 核苷酸序列分析。

The studies proposed in this grant application exemplify a continuation and extension of our ongoing work on the isolation, characterization and expression of new families of endogenous retroviruses. To this end, we plan to isolate and characterize a purportedly novel class of human endogenous retroviruses that we have identified with avian retrovirus-specific genetic probes that we have previously used to identify new classes of avian endogenous retroviruses. Our proposed studies include: (1) isolation of the avian retrovirus-related human endogenous virus family by molecular cloning and characterization by nucleotide sequence analysis; (2) characterization of the extent and nature of expression of this additional family of human endogenous retroviruses in normal and malignant human cell types; and (3) a comparison of this novel endogenous retrovirus family as well as the other previously identified families of human endogenous retroviruses with "C" type virion particles produced by various human tumors including testicular germ cell tumors and differentiating populations of embryonal carcinoma cells to determine whether the "C" type particles produced by these germ cell tumors exhibit any sequence homology to any of the families of human endogenous viruses. The methodologies that we plan to employ to achieve these objectives are, for the most part, already implemented in our laboratory and include a variety of physiochemical, enzymological and hybridization techniques available for the analysis of DNA, RNA, and protein, including nucleotide sequence analysis.