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畸形翅病毒利用宿主精氨酸激酶来增强其在蜜蜂(西方蜜蜂)中的适应性。

Deformed wing virus coopts the host arginine kinase to enhance its fitness in honey bees (Apis mellifera).

作者信息

Becchimanzi Andrea, De Leva Giovanna, Mattossovich Rosanna, Camerini Serena, Casella Marialuisa, Jesu Giovanni, Di Lelio Ilaria, Di Giorgi Sabrina, de Miranda Joachim R, Valenti Anna, Gigliotti Silvia, Pennacchio Francesco

机构信息

Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy.

BAT Center-Interuniversity Center for Studies On Bioinspired Agro-Environmental Technology, University of Naples Federico II, Naples, Italy.

出版信息

BMC Biol. 2025 Jan 13;23(1):12. doi: 10.1186/s12915-025-02117-x.

DOI:10.1186/s12915-025-02117-x
PMID:39800727
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11727705/
Abstract

BACKGROUND

Deformed wing virus (DWV) is a major honey bee pathogen that is actively transmitted by the parasitic mite Varroa destructor and plays a primary role in Apis mellifera winter colony losses. Despite intense investigation on this pollinator, which has a unique environmental and economic importance, the mechanisms underlying the molecular interactions between DWV and honey bees are still poorly understood. Here, we report on a group of honey bee proteins, identified by mass spectrometry, that specifically co-immunoprecipitate with DWV virus particles.

RESULTS

Most of the proteins identified are involved in fundamental metabolic pathways. Among the co-immunoprecipitated proteins, one of the most interesting was arginine kinase (ArgK), a conserved protein playing multiple roles both in physiological and pathological processes and stress response in general. Here, we investigated in more detail the relationship between DWV and this protein. We found that argK RNA level positively correlates with DWV load in field-collected honey bee larvae and adults and significantly increases in adults upon DWV injection in controlled laboratory conditions, indicating that the argK gene was upregulated by DWV infection. Silencing argK gene expression in vitro, using RNAi, resulted in reduced DWV viral load, thus confirming that argK upregulation facilitates DWV infection, likely through interfering with the delicate balance between metabolism and immunity.

CONCLUSIONS

In summary, these data indicate that DWV modulates the host ArgK through transcriptional regulation and cooptation to enhance its fitness in honey bees. Our findings open novel perspectives on possible new therapies for DWV control by targeting specific host proteins.

摘要

背景

变形翅病毒(DWV)是一种主要的蜜蜂病原体,由寄生螨狄斯瓦螨积极传播,在西方蜜蜂冬季蜂群损失中起主要作用。尽管对这种具有独特环境和经济重要性的传粉者进行了深入研究,但DWV与蜜蜂之间分子相互作用的潜在机制仍知之甚少。在此,我们报告了一组通过质谱鉴定的蜜蜂蛋白质,它们能与DWV病毒颗粒特异性共免疫沉淀。

结果

鉴定出的大多数蛋白质参与基本代谢途径。在共免疫沉淀的蛋白质中,最有趣的一种是精氨酸激酶(ArgK),它是一种保守蛋白质,在生理和病理过程以及一般应激反应中都发挥多种作用。在此,我们更详细地研究了DWV与这种蛋白质之间的关系。我们发现,在野外采集的蜜蜂幼虫和成虫中,argK RNA水平与DWV载量呈正相关,并且在受控实验室条件下给成虫注射DWV后,其水平显著升高,这表明argK基因因DWV感染而上调。在体外使用RNA干扰沉默argK基因表达,导致DWV病毒载量降低,从而证实argK上调促进DWV感染,可能是通过干扰代谢与免疫之间的微妙平衡。

结论

总之,这些数据表明DWV通过转录调控和利用宿主ArgK来增强其在蜜蜂中的适应性。我们的发现为通过靶向特定宿主蛋白控制DWV的可能新疗法开辟了新视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/f692ea051260/12915_2025_2117_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/0c13f885a62b/12915_2025_2117_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/d504bc742e7f/12915_2025_2117_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/8b589a3ccb10/12915_2025_2117_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/b3b8a5e94ba1/12915_2025_2117_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/f692ea051260/12915_2025_2117_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/0c13f885a62b/12915_2025_2117_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/d504bc742e7f/12915_2025_2117_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/8b589a3ccb10/12915_2025_2117_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/b3b8a5e94ba1/12915_2025_2117_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6175/11727705/f692ea051260/12915_2025_2117_Fig5_HTML.jpg

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本文引用的文献

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A comprehensive review of arginine kinase proteins: What we need to know?精氨酸激酶蛋白的全面综述:我们需要了解什么?
Biochem Biophys Rep. 2024 Oct 8;40:101837. doi: 10.1016/j.bbrep.2024.101837. eCollection 2024 Dec.
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Shift in virus composition in honeybees () following worldwide invasion by the parasitic mite and virus vector .在寄生螨和病毒载体全球入侵后蜜蜂体内病毒组成的变化()
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Processing of the 3C/D Region of the Deformed Wing Virus (DWV).
畸形翼病毒(DWV)3C/D 区的加工。
Viruses. 2023 Nov 29;15(12):2344. doi: 10.3390/v15122344.
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Effects of Deformed Wing Virus-Targeting dsRNA on Viral Loads in Bees Parasitised and Non-Parasitised by .变形翅膀病毒靶向 dsRNA 对被. 寄生和未被寄生的蜜蜂病毒载量的影响。
Viruses. 2023 Nov 15;15(11):2259. doi: 10.3390/v15112259.
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Immunoprecipitation Followed by Mass Spectrometry: An Approach for Identifying Host-Viral Protein-Protein Interactions.免疫沉淀联合质谱分析:一种鉴定宿主-病毒蛋白-蛋白相互作用的方法。
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Restoration of energy homeostasis under oxidative stress: Duo synergistic AMPK pathways regulating arginine kinases.氧化应激下能量稳态的恢复:双协同 AMPK 通路调节精氨酸激酶。
PLoS Genet. 2023 Aug 3;19(8):e1010843. doi: 10.1371/journal.pgen.1010843. eCollection 2023 Aug.
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Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies.钾离子通道作为降低病毒感染和蜜蜂死亡率的分子靶标。
Virol J. 2023 Jun 22;20(1):134. doi: 10.1186/s12985-023-02104-0.
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Serine-arginine protein kinases and their targets in viral infection and their inhibition.丝氨酸-精氨酸蛋白激酶及其在病毒感染中的靶标及其抑制。
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Interaction between the VP2 protein of deformed wing virus and host snapin protein and its effect on viral replication.残翅病毒VP2蛋白与宿主小突触泡蛋白的相互作用及其对病毒复制的影响。
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The ProteomeXchange consortium at 10 years: 2023 update.蛋白质组交换联盟成立十周年:2023 年更新。
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