Molecular impact of Deformed wing virus type A in the honey bee brain.

Crop pollination by the western honey bee Apis mellifera is vital to agriculture but threatened by alarmingly high levels of colony mortality, especially in Europe and the US. Colony loss is due, in part, to the high viral loads of Deformed wing virus (DWV), transmitted by the ectoparasitic mite Varroa destructor, especially throughout the overwintering period of a honey bee colony. Covert DWV infection is commonplace and has been causally linked to precocious foraging, which itself has been linked to colony loss. Taking advantage of four brain transcriptome studies that unexpectedly revealed evidence of covert DWV-A infection, we set out to explore whether this effect is due to DWV-A mimicking naturally occurring changes in brain gene expression that are associated with behavioral maturation. Consistent with this hypothesis, we found that brain gene expression profiles of DWV-A infected bees resembled those of foragers, even in samples that were much younger than typical foragers. In addition, transcriptional regulatory network analysis revealed a positive association between DWV-A infection and transcription factors previously associated with honey bee foraging behavior. Surprisingly, single-cell RNA-Sequencing implicated glia, not neurons, in this effect; there are relatively few glial cells in the insect brain and they are rarely associated with behavioral plasticity. Covert DWV-A infection also has been linked to impaired learning, which together with precocious foraging can lead to increased occurrence of bees from one colony mistakenly joining another, especially under crowded modern apiary conditions. Together, these findings support a mechanistic link by which DWV-A may manipulate host behavior to facilitate horizontal transmission.

西方蜜蜂（Apis mellifera）为农作物授粉对农业至关重要，但蜂群高死亡率的问题令人担忧，该授粉服务因此受到严重威胁，尤其在欧洲与美国地区。蜂群损失的部分原因在于变形翅病毒（Deformed wing virus, DWV）的高病毒载量，该病毒由体外寄生螨瓦螨（Varroa destructor）传播，尤其在蜂群越冬期间更为严重。隐蔽性DWV感染十分普遍，且已被证实与早熟采粉行为存在因果关联，而此种采粉行为本身又与蜂群损失密切相关。
我们依托四项意外发现了隐蔽性变形翅病毒A型（Deformed wing virus A, DWV-A）感染证据的脑转录组研究，旨在探究此种效应是否由DWV-A模拟了与行为成熟相关的天然脑基因表达变化所引发。与该假说相符，我们发现DWV-A感染蜜蜂的脑基因表达谱与采粉蜂高度相似，即便在远早于典型采粉蜂年龄的样本中亦是如此。此外，转录调控网络分析显示，DWV-A感染与此前已被证实与蜜蜂采粉行为相关的转录因子呈正相关。
令人意外的是，单细胞RNA测序（single-cell RNA-Sequencing）表明，此种效应涉及神经胶质细胞而非神经元；昆虫脑中的神经胶质细胞数量相对稀少，且极少与行为可塑性相关联。隐蔽性DWV-A感染还与学习能力受损存在关联，而此种损伤与早熟采粉行为一同，可能导致单个蜂群的蜜蜂误加入其他蜂群的概率上升，尤其是在现代养蜂场拥挤的环境条件下。
综上，这些发现支持了一种机制性关联：DWV-A或可通过操控宿主行为以促进病毒的水平传播。