Mosquito host background influences microbiome-ZIKV interactions in field and laboratory-rearedAedes aegypti
Authors: Cansado-Utrilla Cintia , Saldaña Miguel A. , Golovko George , Khanipov Kamil , Wild Alex L. , Brettell Laura E. , Weaver Scott C. , Heinz Eva , Hughes Grant L. 
Published: February 2025

AbstractThe mosquito microbiota represents an intricate assemblage of microorganisms, comprising bacteria, fungi, viruses, and protozoa. Factors modulating microbiome abundance and composition include host genetic background, environmental parameters, and pathogen exposure. Conversely, the microbiome profoundly influences pathogen infection of the mosquito host and thus harbours considerable potential to impact the transmission of vector-borne diseases. As such, there is a growing interest in using the microbiome in novel vector-control strategies, including exploiting the natural ability of some microbes to interfere with infection of the vectors by pathogens. However, before novel microbiome-based vector control approaches can move towards translation, a more complete understanding of the interactions between mosquitoes, their microbiome, and the pathogens they transmit, is required to better appreciate how variation in the microbiome of field mosquitoes affects these interactions. To examine the impact of the host background and the associated diversity of microbiomes within distinct hosts, but without artificially manipulating the microbiome, we exposed several laboratory-reared and field-collectedAedes aegyptimosquito lines to Zika virus (ZIKV) and correlated their microbial load and composition to pathogen exposure and viral infection success. We observed significant differences in ZIKV exposure outcomes between the different mosquito lines and their associated microbiomes, and found that ZIKV alteration of the microbiomes was distinct in different lines. We also identified microbial taxa correlating with either ZIKV infection or a lack of infection. In summary, our study provides novel insights into the variability of pathogen interactions within the mosquito holobiont. A more complete understanding of which factors influence the tripartite interactions betweenAedesmosquitoes, their microbiome, and arboviral pathogens, will be critical for the development of microbial-based interventions aimed at reducing vector-borne disease burden.Author summary.The mosquito microbiome composition differs within an individual across its development, as well as between individual mosquitoes at the same developmental stage, and between spatially or genomically different mosquito populations. The microbiome is highly relevant for the ability of mosquitoes to transmit pathogens. Furthermore, certain microbes have been shown to influence pathogen infection of the mosquito, while conversely, infection with a pathogen can alter the mosquito microbiome. However, we have a poor understanding how universally conserved these pathogen-related effects observed in a specific host-microbiome combination are in different mosquito populations with their respective microbiomes. To address this, we infected different mosquito lines, either reared in the laboratory or caught in the field and examined the microbiomes after exposure to Zika virus (ZIKV) compared to unchallenged microbiomes. We also examined how the virus infection progressed in different mosquito lines and correlations with further microbiome changes. The observed microbiome responses differed between host lines, potentially due to either different microbiomes associated with the respective hosts. Alternatively, the host may respond differently to the viral infection, which subsequently alters the microbiome in a distinct manner, or a combination of host and microbiome effects may occur. As microbes are being evaluated for novel approaches to control mosquito-borne disease, our findings are highly relevant to contribute to a more complete understanding of host-microbe interactions which will be critical to develop these approaches. Variation of the microbiome of different mosquito lines need to be considered in experimental designs and when interpreting results from specific studies. It is especially relevant for deployment of interventions in the field where microbial variability is known to be higher and where variation is observed between mosquito populations.