Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes.

Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes.
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DOI:
10.1186/1471-2164-12-625
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发表时间:
2011-12-20
期刊:
影响因子:
4.4
通讯作者:
Chang Y
Chang Y
中科院分区:
生物学2区
文献类型:
--
作者:
Dresang LR;Teuton JR;Feng H;Jacobs JM;Camp DG 2nd;Purvine SO;Gritsenko MA;Li Z;Smith RD;Sugden B;Moore PS;Chang Y

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卡波西肉瘤相关疱疹病毒(KSHV)和爱泼斯坦-巴尔病毒(EBV)分别是引起原发性渗出性淋巴瘤(PEL)和伯基特淋巴瘤(BL)的相关人类肿瘤病毒。在自然感染的癌细胞中表达的病毒基因有助于疾病的发病机制;了解哪些病毒基因表达对于了解这些病毒如何导致癌症至关重要。为了评估病毒基因的表达,我们使用高分辨率分离和质谱仪结合定制的平铺阵列,在潜伏和裂解培养条件下比对了三个PEL和两个BL细胞系的病毒蛋白质组和转录本。在操纵病毒生命周期的过程中,大多数病毒基因都能在转录本和/或蛋白质水平上得到有效检测。总体而言,表达的病毒蛋白和转录本的相关性在验证和提供潜伏/裂解病毒基因表达的正交数据方面具有很强的互补性。我们的方法还在KSHV和EBV中发现了新的病毒基因,并扩展了病毒基因组注释。在转录本和蛋白质水平上都证实了几个以前未被鉴定的基因。这种结合蛋白质组和转录组测量的系统生物学方法提供了病毒基因表达的全面视图,这是单独使用每种方法无法获得的。结合病毒转录本检测病毒蛋白是建立病毒-疾病关系的一种潜在的有效方法。
Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.
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