急性转化型滤过性病原体FAFU01株的鉴定及其致瘤机制研究

It was known that the acutely transforming strain of retrovirus can induce the acute transformation in chicken embryo fibroblast (CEF).A strain of virus was isolated from the clinicial tumor tissue of some broiler breeder. It was found that this virus isolate acutely transformed CEF in vitro and incubation of this isolate in the chicken embryos could induce the hemangioma on the body surface.However the ELISA test of the group-specific antigen, p27, and specific PCR test for different subgroups ALSV showed both negative results. It can be concluded that the pathogen is some unknown virus. We plan to reveal the etiology character including the morphological structure, physicochemical characteristics and the tumorigenesis peculiarity, as well as the the tumorigenesis mechanism of the virus, in order to explain the molecular mechanism of acute transformation of the isolate and to provide the basis of the clinical prevention and control of the spread of the associated acute phymatosis.

目前已知的能够在体外急性转化鸡胚成纤维细胞（CEF）的病毒主要为反转录病毒中的某些急性转化型毒株，本课题组从肉种鸡肿瘤组织中分离到一株滤过性病原体，发现该病原体可急性转化CEF，并可能与鸡急性血管瘤有关。然而对该病原体转化细胞进行禽白血病/肉瘤病毒(ALSV)群特异性抗原p27的ELISA检测和针对不同亚群ALSV的鉴定PCR检测，结果表明均为阴性，基于前人研究，认为该病原体为某种未知的转化因子，拟对该病原体的形态结构、理化特性等病原学特征，病毒体内外转化和致瘤特性及病毒的致瘤相关蛋白等致瘤机理进行系统研究，以期揭示该病原体急性致瘤的分子机理，为临床防控此急性致瘤病原体的蔓延提供科学依据。

本项目通过对滤过性病原体进行IFA、PCR及全基因组序列分析鉴定，确定该病原体为一株具有B亚群 gp85基因特性和J亚群 LTR特性的复制完全型重组反转录病毒。对该毒株进行致瘤特性研究发现：该毒株先天性感染和早期水平感染可导致显著生长抑制和体液免疫抑制(P<0.05)；病毒主要亲嗜肾脏、法氏囊；至11w可发现先天性感染动物内脏中出现大小不等的淋巴细胞瘤，表现出强致瘤能力。为揭示该毒株的致瘤机理，对其感染组织进行差异转录组学研究，发现PPAR、Jak/STAT信号通路和脂肪细胞因子信号通路等显著参与到病毒的致病过程(P<0.05)；进一步研究发现，组织中CNTFRa与病毒复制呈现出极显著相关关系(r=0.656, P<0.001)，参与到病毒与宿主的互作。该研究为揭示该病毒的致瘤致病机制提供了重要数据，为防控该病提供科学依据。

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