Marek's disease virus encodes microRNAs that map to meq and the latency-associated transcript
Marek's disease virus encodes microRNAs that map to meq and the latency-associated transcript
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DOI：
10.1128/jvi.00831-06
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Morgan, Robin W.
中科院分区：
文献类型：
--
作者：
Burnside, Joan;Bernberg, Erin;Morgan, Robin W.
MicroRNAs(MiRNAs)是一类小的(类似于22个核苷酸的)调节分子，可以阻断靶mRNAs的翻译或诱导其降解。它们已经在包括病毒在内的广泛的生物体中被发现。特别是，致癌的伽马疱疹病毒Kaposi的肉瘤疱疹病毒和Epstein-Barr病毒编码的miRNAs可能调节病毒或宿主基因。为了确定鸡马立克氏病病毒(MDV)是否编码miRNAs，我们从NIM感染的鸡胚胎成纤维细胞(CEF)中分离了小RNA，并利用454生命科学测序技术获得了13679个候选宿主和病毒小RNA的序列。发现了8个miRNAs，其中5个位于MEQ癌基因两侧，3个映射到基因组的潜伏期相关转录(LAT)区域。MEQ基因是MDV致病血清型特有的基因，在潜伏和转化过程中转录活跃，而MDV基因组的LAT区与即刻早期基因ICP4反义。二级结构分析预测，miRNAs侧翼区域可以形成发夹前体。Northern印迹分析证实，所有miRNAs在NIM感染的CEF、MDV诱导的肿瘤和MDV淋巴母细胞系中都有表达。我们认为MDV miRNAs可能参与了MDV的致病过程，并参与了MDV诱导的鸡T细胞转化。
MicroRNAs (miRNAs) are a class of small (similar to 22-nucleotide) regulatory molecules that block translation or induce degradation of target mRNAs. These have been identified in a wide range of organisms, including viruses. In particular, the oncogenic gammaherpesviruses Kaposi's sarcoma herpesvirus and Epstein-Barr virus encode miRNAs that could potentially regulate either viral or host genes. To determine if Marek's disease virus (MDV), an oncogenic alphaherpesvirus of chickens, encodes miRNAs, we isolated small RNAs from NIM-infected chicken embryo fibroblasts (CEF) and used the 454 Life Sciences sequencing technology to obtain the sequences of 13,679 candidate host and viral small RNAs. Eight miRNAs were found, five of which flank the meq oncogene and three that map to the latency-associated transcript (LAT) region of the genome. The meq gene is unique to pathogenic serotypes of MDV and is transcriptionally active during latency and transformation, and the LAT region of the MDV genome is antisense to the immediate-early gene ICP4. Secondary structure analysis predicted that the regions flanking the miRNAs could form hairpin precursors. Northern blot analysis confirmed expression of all miRNAs in NIM-infected CEF, MDV-induced tumors, and MDV lymphoblastoid cell lines. We propose that the MDV miRNAs function to enable MDV pathogenesis and contribute to MDV-induced transformation of chicken T cells.