Mejías Sebastián, Jiménez Natalia E, Conca Carlos, Salgado J Cristian, Gerdtzen Ziomara P
Center for Biotechnology and Bioengineering (CeBiB), University of Chile, Santiago, Santiago, Chile.
Millennium Nucleus Marine Agronomy of Seaweed Holobionts (MASH), Puerto Montt, Chile.
Front Cell Infect Microbiol. 2025 Apr 28;15:1538459. doi: 10.3389/fcimb.2025.1538459. eCollection 2025.
The mosquito is the main vector of arboviral diseases such as dengue and imposes a global health burden. A promising control strategy is to infect populations with , a genus of intracellular bacteria capable of blocking arboviral infections. Enhancing and preserving the efficacy of this method will depend on a solid mechanistic knowledge of the symbiosis. By identifying differences between -infected and uninfected , previous transcriptomic studies proposed a wide range of symbiotic interactions, but a systematic identification of consistent effects across datasets is still missing.
To identify genes and functions consistently affected by , we performed differential expression and functional enrichment analysis on published transcriptomic datasets, followed by a meta-analysis of the obtained using the maxP method. Six datasets were retrieved from Gene Expression Omnibus, Sequence Read Archive and ArrayExpress (last searched in July 2024, considering lack of replication as the exclusion criteria). After discarding one dataset from AlbB-infected cell line due to poor mapping to the genome, the data comprised adult female heads, muscles, carcasses, midguts and bodies, and Wolbachia strains wMel and wMelPop.
Meta-analysis revealed 10 and 21 consistently down- and upregulated host genes, some of which have escaped the focus of previous research, including the consistently downregulated exonuclease which has a pro-dengue virus homolog in . At the function level, we found consistent upregulation of electron transport chain (ETC), carbohydrate transport and serine-type peptidase activity and inhibition, and downregulation of DNA replication. ETC upregulation suggests an alternative mechanism for Wolbachia's induction of antiviral oxidative stress, previously attributed to dual- and NADPH-oxidases which here showed downregulation or no regulation. Through analysis of previously published datasets, this work identifies promising molecular and functional targets for future studies aimed at elucidating the most fundamental mechanisms of the symbiosis.
蚊子是登革热等虫媒病毒疾病的主要传播媒介，给全球健康带来负担。一种有前景的控制策略是用沃尔巴克氏体（Wolbachia）感染蚊子种群，沃尔巴克氏体是一类能够阻断虫媒病毒感染的细胞内细菌。增强并维持该方法的效果将取决于对这种共生关系的深入机制了解。通过识别感染沃尔巴克氏体和未感染的蚊子之间的差异，先前的转录组学研究提出了广泛的共生相互作用，但仍缺乏对各数据集一致效应的系统识别。
为了识别受沃尔巴克氏体持续影响的蚊子基因和功能，我们对已发表的转录组数据集进行了差异表达和功能富集分析，随后使用maxP方法对所得结果进行荟萃分析。从基因表达综合数据库（Gene Expression Omnibus）、序列读取存档库（Sequence Read Archive）和ArrayExpress数据库中检索到六个数据集（最后一次搜索时间为2024年7月，将缺乏重复数据作为排除标准）。由于与蚊子基因组的比对效果不佳，我们舍弃了来自感染AlbB细胞系的一个数据集，最终的数据包括成年雌性蚊子的头部、肌肉、尸体、中肠和身体，以及沃尔巴克氏体菌株wMel和wMelPop。
荟萃分析揭示了分别有10个和21个宿主基因持续下调和上调，其中一些基因此前未受到研究关注，包括持续下调的核酸外切酶，该酶在蚊子中有登革热病毒同源物。在功能层面，我们发现电子传递链（ETC）、碳水化合物转运和丝氨酸型肽酶活性持续上调且受到抑制，DNA复制下调。ETC上调表明沃尔巴克氏体诱导抗病毒氧化应激存在另一种机制，此前该机制归因于双氧化酶和NADPH氧化酶，而在本研究中它们表现为下调或无调控。通过对先前发表的数据集进行分析，本研究确定了有前景的分子和功能靶点，可供未来研究用于阐明沃尔巴克氏体共生关系的最基本机制。
