Dishevelled Has Anti-Viral Activity in Rift Valley Fever Virus Infected Aedes aegypti.
Dishevelled Has Anti-Viral Activity in Rift Valley Fever Virus Infected Aedes aegypti.
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DOI：
10.3390/v15112140
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发表时间：
2023-10-24
期刊：
影响因子：
--
通讯作者：
Campbell CL
中科院分区：
文献类型：
--
作者：
Smith CB;Hodges NF;Kading RC;Campbell CL
伊蚊属和库蚊属的蚊子是裂谷热病毒（RVFV）的载体，该病毒在非洲和沙特阿拉伯定期流行。影响RVFV传输动力学的因素没有很好地表征。为了解决这一问题，我们询问蚊子宿主的信号转导反应，通过分析差异表达的基因（DEG）在两种蚊子的RVFV载体能力有显着差异：埃及伊蚊（Aae，低能力）和跗库蚊（Cxt，高能力）。研究了与三种不同信号通路相关的蚊子宿主转录物。评估了来自无翅（Wg，WNT-β-连环蛋白）途径的选定基因，其是细胞增殖和分化的保守调节因子。其中之一，凌乱（DSH），差异调节WNT和JNK（c-Jun N-末端激酶）途径的进展/抑制。还评估了JNK信号传导途径的负调节因子puckered。最后，Janus激酶/信号转导和转录激活因子（JAK-STAT）对先天免疫很重要;在这种情况下，我们测试了无圆顶水平。在此，个体Aae和Cxt通过口服血粉暴露于RVFV MP-12并保持14天。在Aae和Cxt中均观察到DEG的稳健降低。特别地，Aae DSH表达而不是Cxt DSH表达与攻击后14天（dpc）病毒RNA的存在/不存在相关。病毒拷贝数与aaeDSH表达呈负相关。与对照组相比，DSH沉默在3 dpc时导致病毒拷贝数增加，这与aaeDSH在抗病毒免疫中的作用一致。对感兴趣的基因的顺式调控区的分析揭示了这些途径的上游调控的线索。
Mosquitoes in the genera Aedes and Culex are vectors of Rift Valley fever virus (RVFV), which emerges in periodic epidemics in Africa and Saudi Arabia. Factors that influence the transmission dynamics of RVFV are not well characterized. To address this, we interrogated mosquito host-signaling responses through analysis of differentially expressed genes (DEGs) in two mosquito species with marked differences in RVFV vector competence: Aedes aegypti (Aae, low competence) and Culex tarsalis (Cxt, high competence). Mosquito–host transcripts related to three different signaling pathways were investigated. Selected genes from the Wingless (Wg, WNT-beta-catenin) pathway, which is a conserved regulator of cell proliferation and differentiation, were assessed. One of these, dishevelled (DSH), differentially regulates progression/inhibition of the WNT and JNK (c-Jun N-terminal Kinase) pathways. A negative regulator of the JNK-signaling pathway, puckered, was also assessed. Lastly, Janus kinase/signal transducers and activators of transcription (JAK-STAT) are important for innate immunity; in this context, we tested domeless levels. Here, individual Aae and Cxt were exposed to RVFV MP-12 via oral bloodmeals and held for 14 days. Robust decreases in DEGs in both Aae and Cxt were observed. In particular, Aae DSH expression, but not Cxt DSH, was correlated to the presence/absence of viral RNA at 14 days post-challenge (dpc). Moreover, there was an inverse relationship between the viral copy number and aaeDSH expression. DSH silencing resulted in increased viral copy numbers compared to controls at 3 dpc, consistent with a role for aaeDSH in antiviral immunity. Analysis of cis-regulatory regions for the genes of interest revealed clues to upstream regulation of these pathways.
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影响因子：
14.9
作者：
Lawson, Daniel;Arensburger, Peter;Atkinson, Peter;Besansky, Nora J;Bruggner, Robert V;Butler, Ryan;Campbell, Kathryn S;Christophides, George K;Christley, Scott;Dialynas, Emmanuel;Emmert, David;Hammond, Martin;Hill, Catherine A;Kennedy, Ryan C;Lobo, Neil F;MacCallum, M Robert;Madey, Greg;Megy, Karine;Redmond, Seth;Russo, Susan;Severson, David W;Stinson, Eric O;Topalis, Pantelis;Zdobnov, Evgeny M;Birney, Ewan;Gelbart, William M;Kafatos, Fotis C;Louis, Christos;Collins, Frank H
通讯作者：
Collins, Frank H
影响因子：
5.4
作者：
Harmon B;Bird SW;Schudel BR;Hatch AV;Rasley A;Negrete OA
通讯作者：
Negrete OA
影响因子：
--
作者：
Schweizer L;Varmus H
通讯作者：
Varmus H
影响因子：
4.2
作者：
Campbell CL;Keene KM;Brackney DE;Olson KE;Blair CD;Wilusz J;Foy BD
通讯作者：
Foy BD
影响因子：
64.8
作者：
Bhanot, P;Brink, M;Nusse, R
通讯作者：
Nusse, R