Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
J Virol. 2012 Dec;86(23):12849-60. doi: 10.1128/JVI.01113-12. Epub 2012 Sep 19.
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.
在过去的 5 年中，一种亚群 J 型禽白血病病毒（ALV-J）的非典型临床暴发在中国鸡群中流行，该病毒在其 3'非翻译区（3'UTR）中含有独特的 205 个核苷酸缺失。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。第一株病毒是一株含有 3'UTR 中 205 个核苷酸缺失的 ALV-J 中国分离株（命名为 HLJ09SH01）。第二株病毒是嵌合克隆，其 3'UTR 包含与 ALV-J 原型病毒区域相对应的 205 个核苷酸序列。研究了拯救病毒（rHLJ09SH01 和 rHLJ09SH01A205）的复制和致病性。与 rHLJ09SH01A205 相比，rHLJ09SH01 在体外和体内显示出适度的生长优势，并且在蛋鸡和肉鸡中表现出更高的致癌率和致死率。在早期胚胎血管发育过程中，rHLJ09SH01 诱导的血管内皮生长因子 A（VEGF-A）和血管内皮生长受体亚型 2（VEGFR-2）表达高于 rHLJ09SH01A205，但当将表达水平归一化为病毒水平时，这种表达增加消失了。这一发现表明，VEGF-A 和 VEGFR-2 的表达与病毒复制有关，也可能代表了 ALV-J 致癌潜力的新分子机制。总的来说，我们的研究结果不仅表明 ALV-J 基因组中独特的 205 个核苷酸缺失在中国自然发生并导致致病性增加，而且还指出了 ALV-J 诱导致癌性的可能机制。
