Marek's disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication
Marek's disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication
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DOI：
10.1073/pnas.0404508101
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发表时间：
2004-08-10
影响因子：
11.1
通讯作者：
Reddy, SM
中科院分区：
文献类型：
--
作者：
Lupiani, B;Lee, LF;Reddy, SM
马立克氏病病毒（MDV）引起鸡的急性淋巴细胞增生性疾病，导致内脏器官和周围神经的T细胞淋巴瘤。早期的研究已经确定，致癌性血清型1 MDV的重复区域编码一种基本亮氨酸拉链蛋白Meq，其结构类似于Jun/Fos转录激活因子家族。Meq在mdv诱导的肿瘤细胞中一致表达，并被认为是mdv相关的癌基因。为了研究Meq的功能，我们从一种非常毒力的MDV毒株的基因组中删除了Meq基因的两个拷贝，产生了rMd5DeltaMeq病毒。培养成纤维细胞的生长曲线表明Meq是体外病毒复制所必需的。在体内，Meq在淋巴器官和羽毛滤泡上皮中的复制也未受到损害，这表明Meq在鸡溶菌感染中是不可缺少的。外周血淋巴细胞rMd5DeltaMeq病毒的再激活减少，表明Meq参与了潜伏期，但不是必需的。发病机制实验表明，rMd5DeltaMeq病毒在鸡体内被完全减毒，因为感染的鸡没有发生马立克病相关淋巴瘤，这表明Meq参与了淋巴细胞转化。一种还原病毒恢复了meq基因的表达，显示出与亲本病毒相似的特性，证实了meq参与了鸡的转化，但不参与裂解复制。
Marek's disease virus (MDV) causes an acute lymphoproliferative disease in chickens, resulting in T cell lymphomas in visceral organs and peripheral nerves. Earlier studies have determined that the repeat regions of oncogenic serotype 1 MDV encode a basic leucine zipper protein, Meq, which structurally resembles the Jun/Fos family of transcriptional activators. Meq is consistently expressed in MDV-induced tumor cells and has been suggested as the MDV-associated oncogene. To study the function of Meq, we have generated an rMd5DeltaMeq virus by deleting both copies of the meq gene from the genome of a very virulent strain of MDV. Growth curves in cultured fibroblasts indicated that Meq is dispensable for in vitro virus replication. in vivo replication in lymphoid organs and feather follicular epithelium was also not impaired, suggesting that Meq is dispensable for lytic infection in chickens. Reactivation of the rMd5DeltaMeq virus from peripheral blood lymphocytes was reduced, suggesting that Meq is involved but not essential for latency. Pathogenesis experiments showed that the rMd5DeltaMeq virus was fully attenuated in chickens because none of the infected chickens developed Marek's disease-associated lymphomas, suggesting that Meq is involved in lymphocyte transformation. A revertant virus that restored the expression of the meq gene, showed properties similar to those of the parental virus, confirming that Meq is involved in transformation but not in lytic replication in chickens.