A 205-Nucleotide Deletion in the 3′ Untranslated Region of Avian Leukosis Virus Subgroup J, Currently Emergent in China, Contributes to Its Pathogenicity
A 205-Nucleotide Deletion in the 3′ Untranslated Region of Avian Leukosis Virus Subgroup J, Currently Emergent in China, Contributes to Its Pathogenicity
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DOI：
10.1128/jvi.01113-12
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发表时间：
2012-12-01
影响因子：
5.4
通讯作者：
Wang, Xiaomei
中科院分区：
文献类型：
--
作者：
Wang, Qi;Gao, Yulong;Wang, Xiaomei
J亚群禽白血病病毒（ALV-J）3'非翻译区（3' UTR）有一个205个核苷酸的缺失，在近5年来在我国鸡群中发生了一次非典型临床流行。为了确定205个核苷酸缺失在ALV-J致病性中的作用，构建并拯救了一对病毒。第一个病毒是ALV-J中国分离株（命名为HLJ 09 SH 01），其在3' UTR中含有205个核苷酸的缺失。第二种病毒是嵌合克隆，其中3' UTR含有对应于ALV-J原型病毒区域的205个核苷酸序列。对拯救病毒（rHLJ 09 SH 01和rHLJ 09 SH 01 A205）的复制和致病性进行了研究。与rHLJ 09 SH 01 A205相比，rHLJ 09 SH 01在体外和体内表现出中等的生长优势，并且在蛋鸡和肉鸡中表现出较高的致瘤率和致死率。在早期胚胎血管发育过程中，rHLJ 09 SH 01比rHLJ 09 SH 01 A205诱导血管内皮生长因子A（VEGF-A）和血管内皮生长受体亚型2（VEGFR-2）表达增加，但当表达水平标准化为病毒水平时，这种表达增加消失。这一发现表明，VEGF-A和VEGFR-2的表达与病毒复制，也可能代表了一个新的分子机制ALV-J的致癌潜力。总体而言，我们的研究结果不仅表明，独特的205个核苷酸的缺失ALV-J基因组中自然发生在中国，并有助于增加致病性，但也点ALV-J诱导致癌性的可能机制。
In the past 5 years, an atypical clinical outbreak of avian leukosis virus subgroup J (ALV-J), which contains a unique 205-nucleotide deletion in its 3' untranslated region (3' UTR), has become epidemic in chickens in China. To determine the role of the 205-nucleotide deletion in the pathogenicity of ALV-J, a pair of viruses were constructed and rescued. The first virus was an ALV-J Chinese isolate (designated HLJ09SH01) containing the 205-nucleotide deletion in its 3' UTR. The second virus was a chimeric clone in which the 3' UTR contains a 205-nucleotide sequence corresponding to a region of the ALV-J prototype virus. The replication and pathogenicity of the rescued viruses (rHLJ09SH01 and rHLJ09SH01A205) were investigated. Compared to rHLJ09SH01A205, rHLJ09SH01 showed a moderate growth advantage in vitro and in vivo, in addition to exhibiting a higher oncogenicity rate and lethality rate in layers and broilers. Increased vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth receptor subtype 2 (VEGFR-2) expression was induced by rHLJ09SH01 more so than by rHLJ09SH01A205 during early embryonic vascular development, but this increased expression disappeared when the expression levels were normalized to the viral levels. This finding suggests that the expression of VEGF-A and VEGFR-2 is associated with viral replication and may also represent a novel molecular mechanism underlying the oncogenic potential of ALV-J. Overall, our findings not only indicate that the unique 205-nucleotide deletion in the ALV-J genome occurred naturally in China and contributes to increased pathogenicity but also point to the possible mechanism of ALV-J-induced oncogenicity.