Host cell transcriptome profile during wild-type and attenuated dengue virus infection.
Host cell transcriptome profile during wild-type and attenuated dengue virus infection.
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DOI：
10.1371/journal.pntd.0002107
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发表时间：
2013
影响因子：
3.8
通讯作者：
Ooi EE
中科院分区：
文献类型：
--
作者：
Sessions OM;Tan Y;Goh KC;Liu Y;Tan P;Rozen S;Ooi EE
登革病毒1-4型（DENV 1 -4）严重依赖宿主细胞机制来完成其生命周期，同时逃避可能限制其复制效率的宿主反应。这些要求可以解释DENV感染后宿主转录组的大部分广泛基因水平变化。然而，宿主基因功能也通过转录起始位点（TSS）选择和RNA的转录后修饰来调节，从而产生多种基因亚型。这些过程在宿主对登革热感染的反应中所起的作用尚未探讨。在本研究中，我们利用RNA测序（RNAseq）来识别响应DENV 1致病株及其减毒衍生物感染的新型转录变异。RNAseq提供了区分由单个基因产生的各种亚型及其剪接变体所需的信息。我们的数据表明，有大量的先前未表征的TSS和转录后修饰的宿主RNA在广泛的途径和宿主功能响应DENV感染。本研究中鉴定的许多差异表达基因先前已被证明是黄病毒繁殖和/或与DENV基因产物相互作用所需的。我们还表明，人类转录组对野生型DENV或其减毒衍生物感染的反应显着不同。这种对野生型和减毒DENV感染的不同应答表明，替代性加工事件可能是以前未表征的对病毒感染的先天免疫应答的一部分，其在很大程度上被野生型DENV逃避。登革热是全球最常见的虫媒病毒性疾病。持续缺乏有效的治疗源于对疾病发病机制的不完全理解，其中宿主对感染的反应被认为起着核心作用。虽然以前的研究已经描述了登革热病毒感染后总基因表达的变化，但它们无法提供关于宿主RNA细微变化的任何信息。这些变异导致基因异构体的产生，对基因功能产生深远影响。在目前的研究中，我们使用了新开发的RNA测序技术，更准确地询问感染野生型登革病毒或其减毒衍生物后宿主RNA的变化。这项研究的结果表明，宿主RNA对登革热感染的反应存在大量以前未表征的变异。对野生型登革热感染的反应也与疫苗株感染显著不同。这表明宿主RNA的变异构成了宿主对病毒感染的反应的一部分，而野生型登革病毒在很大程度上逃避了这种反应。
Dengue viruses 1–4 (DENV1-4) rely heavily on the host cell machinery to complete their life cycle, while at the same time evade the host response that could restrict their replication efficiency. These requirements may account for much of the broad gene-level changes to the host transcriptome upon DENV infection. However, host gene function is also regulated through transcriptional start site (TSS) selection and post-transcriptional modification to the RNA that give rise to multiple gene isoforms. The roles these processes play in the host response to dengue infection have not been explored. In the present study, we utilized RNA sequencing (RNAseq) to identify novel transcript variations in response to infection with both a pathogenic strain of DENV1 and its attenuated derivative. RNAseq provides the information necessary to distinguish the various isoforms produced from a single gene and their splice variants. Our data indicate that there is an extensive amount of previously uncharacterized TSS and post-transcriptional modifications to host RNA over a wide range of pathways and host functions in response to DENV infection. Many of the differentially expressed genes identified in this study have previously been shown to be required for flavivirus propagation and/or interact with DENV gene products. We also show here that the human transcriptome response to an infection by wild-type DENV or its attenuated derivative differs significantly. This differential response to wild-type and attenuated DENV infection suggests that alternative processing events may be part of a previously uncharacterized innate immune response to viral infection that is in large part evaded by wild-type DENV. Dengue is the most common insect-borne viral disease globally. The continued absence of an effective therapy stems from an incomplete understanding of disease pathogenesis, of which the host response to infection is thought to play a central role. While previous studies have described the changes in total gene expression with dengue virus infection, they have not been able to provide any information on the subtle variations of the host RNA. These variations lead to the production of gene isoforms that can have a profound effect on gene function. In the current study, we have used the newly developed technique of RNA sequencing to more accurately interrogate the variations in the host RNA after infection with a wild-type dengue virus or its attenuated derivative. Findings from this study show that there is an extensive amount of previously uncharacterized variation in host RNA response to dengue infection. The response to infection with the wild-type dengue also differs significantly from infection with the vaccine strain. This suggests that variations in the host RNA comprise a part of the host response to viral infection that is in large part evaded by wild-type dengue viruses.
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影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
3.8
作者：
Le Sommer C;Barrows NJ;Bradrick SS;Pearson JL;Garcia-Blanco MA
通讯作者：
Garcia-Blanco MA
影响因子：
3.8
作者：
Fink J;Gu F;Ling L;Tolfvenstam T;Olfat F;Chin KC;Aw P;George J;Kuznetsov VA;Schreiber M;Vasudevan SG;Hibberd ML
通讯作者：
Hibberd ML
影响因子：
5.4
作者：
Huang, CYH;Butrapet, S;Kinney, RM
通讯作者：
Kinney, RM
DOI：
10.1086/596507
发表时间：
2009-02-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Long HT;Hibberd ML;Hien TT;Dung NM;Van Ngoc T;Farrar J;Wills B;Simmons CP
通讯作者：
Simmons CP