Global cross-talk of genes of the mosquito Aedes aegypti in response to dengue virus infection.
Global cross-talk of genes of the mosquito Aedes aegypti in response to dengue virus infection.
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DOI：
10.1371/journal.pntd.0001385
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发表时间：
2011-11
影响因子：
3.8
通讯作者：
Severson DW
中科院分区：
文献类型：
--
作者：
Behura SK;Gomez-Machorro C;Harker BW;deBruyn B;Lovin DD;Hemme RR;Mori A;Romero-Severson J;Severson DW
埃及伊蚊是登革热病毒（DENV）感染人类的主要媒介，而DENV是世界上大多数亚热带和热带地区最重要的虫媒病毒。感染DENV后的早期时间段定义了决定病毒在蚊子中建立感染的最终成功或失败的关键细胞过程。为了确定参与这些过程的基因，我们在易感和难治性A.在用DENV攻击后的两个关键的早期阶段，埃及菌株。在易感菌株中协调响应DENV感染的基因主要聚集在一个特定的表达模块中，而在难治菌株中，它们分布在四个不同的模块中。易感性反应模块在能量代谢和DNA复制相关基因上表现出明显的偏向性，而难治性反应模块在细胞色素P450和DDT降解基因以及细胞生长和死亡相关基因上表现出明显的偏向性。在易感和难治性蚊子中观察到共同的协调表达基因的核心集，包括与Wnt（Wnt：无翅[wg]和整合1 [int 1]途径）、MAPK（促分裂原活化蛋白激酶）、mTOR（雷帕霉素的哺乳动物靶标）和JAK-STAT（Janus激酶-信号转导和转录激活因子）途径相关的基因。我们的数据揭示了蚊子基因的广泛转录网络，这些基因以模块化的方式表达，以响应DENV感染，并表明成功防御病毒感染需要比宿主病毒更复杂的基因网络。这些可能在关键的早期DENV感染期间蚊子宿主因素之间的全球串扰中发挥重要作用，这些蚊子宿主因素在易感蚊子与难治蚊子中触发适当的宿主行为。登革热病毒主要由埃及伊蚊传播。控制病媒蚊子是预防登革热的主要措施。然而，目前还不清楚该病毒如何感染一些蚊子品系，但不能感染其他难治性品系。为了解决这个问题，我们进行了基于全基因组微阵列的基因表达研究之间的敏感和难治菌株的A。用登革病毒攻击埃及伊蚊以鉴定基因表达模式。我们对早期感染期的分析表明，大量基因以高度协调的方式参与宿主或防御病毒。登革热感染的基因被聚集在7个表达模块中。与感染易感性相关的基因主要集中在一个表达模块中，而与难治性相关的基因分布在四个不同的模块中。一个共同的核心集的基因表达在易感和难治性的个人聚集在两个表达模块。我们确定了可能调节登革热病毒和蚊子之间相容或不相容相互作用的基因和特定途径，最显著的是易感反应中的能量代谢和DNA复制，而非难治反应中的细胞生长和死亡。
The mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in humans, and DENV is the most important arbovirus across most of the subtropics and tropics worldwide. The early time periods after infection with DENV define critical cellular processes that determine ultimate success or failure of the virus to establish infection in the mosquito. To identify genes involved in these processes, we performed genome-wide transcriptome profiling between susceptible and refractory A. aegypti strains at two critical early periods after challenging them with DENV. Genes that responded coordinately to DENV infection in the susceptible strain were largely clustered in one specific expression module, whereas in the refractory strain they were distributed in four distinct modules. The susceptible response module in the global transcriptional network showed significant biased representation with genes related to energy metabolism and DNA replication, whereas the refractory response modules showed biased representation across different metabolism pathway genes including cytochrome P450 and DDT [1,1,1-Trichloro-2,2-bis(4-chlorophenyl) ethane] degradation genes, and genes associated with cell growth and death. A common core set of coordinately expressed genes was observed in both the susceptible and refractory mosquitoes and included genes related to the Wnt (Wnt: wingless [wg] and integration 1 [int1] pathway), MAPK (Mitogen-activated protein kinase), mTOR (mammalian target of rapamycin) and JAK-STAT (Janus Kinase - Signal Transducer and Activator of Transcription) pathways. Our data revealed extensive transcriptional networks of mosquito genes that are expressed in modular manners in response to DENV infection, and indicated that successfully defending against viral infection requires more elaborate gene networks than hosting the virus. These likely play important roles in the global-cross talk among the mosquito host factors during the critical early DENV infection periods that trigger the appropriate host action in susceptible vs. refractory mosquitoes. Dengue virus is primarily transmitted by Aedes aegypti mosquitoes. Control of the vector mosquito is the major practice to prevent dengue. However, it is not well known how the virus can infect some mosquito strains but fail to do so with other refractory strains. To address that question, we conducted whole genome microarray based gene expression studies between susceptible and refractory strains of A. aegypti to identify gene expression patterns following challenge with dengue virus. Our analysis of the early infection periods reveals that a large number of genes are involved in a highly coordinated manner either to host or defend against the virus. Genes responding to dengue infection were clustered in seven expression modules. Genes associated with susceptibility to infection were largely clustered in one expression module, while those associated with refractoriness were distributed in four distinct modules. A common core set of genes expressed in both susceptible and refractory individuals were clustered in two expression modules. We identified genes and specific pathways that potentially regulate compatible or non-compatible interactions between dengue virus and the mosquito, most notably energy metabolism and DNA replication in the susceptible response in contrast to cell growth and death in the refractory response.
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