ONCOGENIC DETERMINANTS OF THE EMERGING ALV-J RETROVIRUS

新兴 ALV-J 逆转录病毒的致癌决定因素

• 批准号: 2743623
• 负责人: KATHLEEN F CONKLIN
• 金额: $ 22.14万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2743623
• 关键词: avian leukosis virus; biochemical evolution; chickens; gene expression; genetic library; genetic polymorphism; genetic recombination; northern blottings; nucleic acid probes; nucleic acid sequence; viral carcinogenesis; virus genetics; virus infection mechanism

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.

J型禽白血病病毒（ALV-J）是一种新的非急性转化型禽白血病病毒， 逆转录病毒表现出几个生物学上有趣的特征。第一、 ALV-J诱导髓性白血病，而大多数其他ALV主要诱导B型白血病 细胞淋巴瘤第二，它有一个包膜基因，指定一个新的亚群 （J）.第三，不同分离株的病毒表现出高度的遗传性 env基因的多样性。第四，ALV-J基因组显示出复杂的 与先前描述的禽流感病毒的关系， 通过内源性和外源性病毒之间的一个或多个重组事件。 在这个提议中的实验被设计来研究几种生物学 ALV-J的特性。内源性ALV-J env相关序列已被 与其他病毒没有高度相关性。实验 （1）确定是否有证据支持假设， 内源性序列有助于感染ALV-J的遗传多样性 病毒和（2）以确定是否存在和/或表达所述病毒， 内源性ALV-J env相关序列与ALV-J env基因表达增加相关， 或降低对ALV-J诱导的恶性肿瘤的易感性。这个建议是 基于对鼠、猫和禽病毒的研究， 内源性病毒序列可以限制或促进病毒诱导的疾病， 独特而有趣的机制。还将进行肿瘤发生研究 研究ALV-J的特异性。ALV-J的两个区域 与其它ALV明显不同的是LTR和env基因。 因此，为了确定这两个区域中的一个或两个是否重要， 为了通过ALV-J诱导骨髓肿瘤，将产生嵌合病毒 ALV-J和传统的B淋巴瘤诱导ALV菌株之间的关系， 分别交换env和LTR区域，随后检测 体内致瘤性。此外，将收集ALV-J诱导的肿瘤， 确定了共同的整合点。