Biology subjects

Merkling, S.

Publications and source records attributed to Merkling, S..

2 recordsLinked to original sources

bioRxiv2025

Stage-resolved metabolomics reveals the methionine cycle as a key regulator of Aedes aegypti development and dengue virus susceptibility

Developmental transitions in the mosquito Aedes aegypti are central to vector competence and disease transmission, yet the underlying metabolic programs remain poorly defined. Here, we use untargeted metabolomics, gene expression analysis, and functional assays to delineate stage-specific metabolic fingerprints across the mosquito life cycle, from egg and larva to pupa and adult. Our profiling of the larval diet reveals comprehensive provisioning of essential nutrients, including B vitamins critical for development. Metabolomic analyses uncover distinct, stage-specific signatures, with the larval stage exhibiting a pronounced enrichment of methionine cycle metabolites and maximal methylation capacity. Notably, while S-adenosylmethionine (SAM) and related metabolites peak in larvae, the transcription of the methionine cycle and histone methyltransferase genes is highest in adults. Functional disruption of the methionine cycle in mosquito cells reveals network-level robustness and regulatory crosstalk within the pathway. However, we also identify a specific vulnerability: silencing the gene adenosylhomocysteinase (ahcy) enhances dengue virus 1 replication and infectious particle production. Collectively, our findings identify the methionine cycle as a metabolic-epigenetic hub that integrates nutrition, development, and viral susceptibility, and highlight the larval stage as a strategic target for novel mosquito-control strategies.

microbiology↗

bioRxiv2024

A Vago-like gene enhances dengue and Zika virus dissemination in Aedes aegypti

Arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, the Aedes aegypti mosquito. In arthropods, genes of the Vago family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of Vago genes upon virus infection in Ae. aegypti is largely unknown. We conducted a phylogenetic analysis of the Vago gene family in Diptera, which led us to focus on a Vago-like gene that we named VLG-1. Using CRISPR/Cas9-mediated gene editing, we generated a VLG-1 mutant line of Ae. aegypti, which revealed a broad impact of VLG-1 on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the VLG-1 mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of VLG-1, virus dissemination throughout the mosquitos body was slightly impaired, albeit not altering virus transmission rates. Our results challenge the conventional understanding of Vago-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.

immunology↗