ONCOGENIC DETERMINANTS OF THE EMERGING ALV-J RETROVIRUS

描述：禽白血病病毒J(ALV-J)是一种新的非急性转化病毒 一种逆转录病毒，表现出几个生物学上有趣的特征。第一, ALV-J诱发髓系白血病，而大多数其他ALV主要诱发B细胞白血病 细胞性淋巴瘤。其次，它有一个包膜基因，它指定了一个新的亚群 (J)。第三，不同的病毒分离株表现出高度的遗传性 Env基因的多样性。第四，ALV-J基因组显示出一个复杂的 与之前描述的禽类病毒的关系，似乎已经出现 通过内源和外源病毒之间的一个或多个重组事件。 这一方案中的实验旨在研究几种生物 ALV-J的性能。内源性ALV-J env相关序列已被 已发现与其他病毒关联度不高的病毒。实验是 建议(1)确定是否有证据支持以下假设 内源性序列对ALV-J感染株遗传多样性的影响 病毒和(2)确定是否存在和/或表达 内源性ALV-J env相关序列与 或降低对ALV-J诱发的恶性肿瘤的易感性。这个建议是 基于对老鼠、猫和禽类病毒的研究，证明 内源性病毒序列可以通过以下方式限制或促进病毒诱导的疾病 独特而有趣的机制。此外，还将进行肿瘤形成研究。 目的探讨ALV-J不寻常的疾病特异性。ALV-J的两个区域 与其他ALV明显不同的是LTR和env基因。 因此，要确定这两个区域中的一个或两个是重要的 对于ALV-J诱导的髓系肿瘤，将产生嵌合病毒 在ALV-J和一种传统的B淋巴瘤诱发ALV株之间， 分别交换env和ltr区域，并随后测试 体内致瘤性。此外，ALV-J诱导的肿瘤将被收集并 标识的公共集成站点。

DESCRIPTION: Avian leukemia virus-J (ALV-J) is a new non-acute transforming retrovirus that exhibits several biologically interesting features. First, ALV-J induces myeloid leukemias whereas most other ALV's induce primarily B cell lymphomas. Second, it has an envelope gene that specifies a novel subgroup (J). Third, different isolates of the virus show a high degree of genetic diversity in the env gene. Fourth, the ALV-J genome shows a complex relationship to previously described avian viruses and appears to have arisen by one or more recombination events between endogenous and exogenous viruses. Experiments in this proposal are designed to investigate several biological properties of ALV-J. Endogenous ALV-J env-related sequences have been identified that are not highly related to other viruses. Experiments are proposed (1) to determine whether evidence supports the hypothesis that these endogenous sequences contribute to the genetic diversity of infecting ALV-J virus and (2) to determine whether the presence and/or expression of the endogenous ALV-J env related sequences are associated with either an increased or decreased susceptibility to ALV-J induced malignancies. This suggestion is based on studies with murine, feline, and avian viruses that demonstrate that endogenous virus sequences can either limit or promote virus-induced disease by distinct and interesting mechanisms. Oncogenesis studies will also be conducted to investigate the unusual disease specificity of ALV-J. Two regions of ALV-J that are clearly distinct from other ALVs are the LTR and the env gene. Therefore, to determine whether either or both of these regions are important for induction of myeloid tumors by ALV-J, chimeric viruses will be generated between ALV-J and a traditional, B-lymphoma inducing strain of ALV that individually exchange the env and LTR regions and subsequently tested for oncogenicity in vivo. In addition, ALV-J induced tumors will be collected and the common integration site identified.