J亚群禽白血病病毒3'非编码区自然缺失205bp影响病毒致病性的研究

Avian leukosis virus subgroup J (ALV-J) causes huge damage and economic loss to the World poultry industry. Recently, outbreaks of this disease happened to the most districts in China. The virus showed higher virulent, diversity of host and tumor type compared with strains isolated before 2008. The sequence analysis showed that a 205 bp natural deletion in the 3'-untranslated region (3'-UTR) of viral genome in most strains. Two strains named rSD1009 and rSD1009A205 were rescued by the infectious cloning technique. A 205 bp natural deletion in 3'-UTR is in the rSD1009 genome while the rSD1009A205 was added the 205 bp artificially. The layer and meet-type chickens were utilized to evaluate the pathogenesis of the two viruses mimicking vertical infection. Information including mortality, the type and incidence of tumor, infection and transmission, ability to vertical infection and the evolution of the viral genome were collected to compare the characteristics between rSD1009 and rSD1009A205 in layer or meet-type chickens. It might answer whether the 205 bp natural deletion in 3'-UTR has the direct correlation with the pathogenicity of ALV-J. And it tried to uncover the mechanism. This study would induce the interest in molecular features in virulence of ALV-J, and offer some suggestions to control and elimination of ALV-J.

J亚群禽白血病是目前严重危害各国养禽业的重要传染病。近年来，J亚群禽白血病在中国大部分地区出现爆发态势，并表现出毒力增强、感染谱增宽、致瘤类型多样化的特点。序列分析显示，大量毒株出现了3'-UTR自然缺失205bp的现象。本项目利用J亚群禽白血病病毒（ALV-J）的感染性克隆平台，构建了3'-UTR自然缺失205bp和人工补全205bp的感染性克隆毒株。两株病毒以模拟垂直感染的方式进行蛋鸡与肉鸡的致病性试验，比较分析两株病毒对蛋鸡和肉鸡的致死率、致瘤率、肿瘤类型、感染和排毒、垂直传播能力及病毒稳定性等多项指标，评估病毒对蛋鸡和肉鸡的致病性差异。明确3'-UTR自然缺失的205bp是否与ALV-J的致病性有关，并探讨其可能的机制。为进一步了解ALV-J毒力的分子基础、更好地防控和净化ALV-J提供一定的依据。

本项目基于ALV-J在我国致病力增强且对我国养禽业造成巨大危害的大背景下，首先对我国鸡群流行的ALV-J毒株进行了分离鉴定及遗传演化分析，发现3’-UTR 205nt的缺失是ALV-J中国蛋鸡毒株基因组的重要进化特点。通过反向遗传和致病性研究，证明3’-UTR 205nt的缺失是ALV-J致病性增强的分子基础。宿主多种因子参与ALV-J的致病过程，VEGF-A和VEGFR-2高水平表达参与ALV-J致病力的形成。本研究阐明了ALV-J在我国鸡群中致病性增强的分子基础和分子机制，同时为ALV-J的防控和净化提供重要科学思路和依据。