DENV2 and ZIKV modulate the feeding behavior of Aedes aegypti by altering the tyrosine-dopamine pathway

ABSTRACT Flaviviruses are known for their neurotropic properties and their long-lasting neurological effects. As mosquito-borne viruses, they can persistently infect the central nervous system of mosquitoes without causing symptoms, yet they can alter the physiology and behavior of these insects. Ho...

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Main Authors: Dongmin Gao, Ruixu Jiang, Zhaoyang Wang, Jichen Niu, Gang Wang, Yicheng Wang, Yan Liang, Yibin Zhu, Gong Cheng
Format: Article
Language:English
Published: American Society for Microbiology 2025-06-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.03968-24
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Summary:ABSTRACT Flaviviruses are known for their neurotropic properties and their long-lasting neurological effects. As mosquito-borne viruses, they can persistently infect the central nervous system of mosquitoes without causing symptoms, yet they can alter the physiology and behavior of these insects. However, the molecular mechanisms by which flaviviruses directly influence mosquito feeding behavior remain largely unexplored. Here, we show that dengue virus serotype 2 (DENV2) and Zika virus (ZIKV) elevate mosquito locomotor activity and blood-feeding propensity throughout the day. Untargeted metabolomics identified increased N-acetyl-L-tyrosine levels in virus-infected mosquito heads, which enhanced locomotor activity and blood-feeding efficiency when injected into Aedes aegypti. Virus infection disrupted the circadian rhythm of tyrosine hydroxylase (Aath), a key dopamine synthesis gene, maintaining its consistent elevation of expression throughout the day. Furthermore, DENV2 and ZIKV perturbed the molecular circadian core oscillator in Ae. aegypti. Additionally, mosquitoes injected with L-3,4-dihydroxyphenylalanine exhibited higher locomotor activity and blood-sucking rates. In contrast, knockdown of Aath reduced blood feeding and decreased infection rates in mice bitten by virus-infected mosquitoes. Collectively, our findings elucidate the molecular mechanisms by which DENV2 and ZIKV modulate the physiology and feeding behavior of Ae. aegypti vectors, thereby facilitating the transmission of these viruses.IMPORTANCEThis study sheds light on how DENV2 and ZIKV affect the feeding behavior of mosquitoes. We discovered the molecular mechanisms that lead to increased movement and blood feeding in mosquitoes by altering neurotransmitter levels and disrupting their internal biological clocks. These findings reveal how these viruses enhance their own transmission by making mosquitoes more active. This research could help in developing strategies to target these processes, ultimately aiding efforts to control the spread of dengue and Zika viruses and reducing the risk of outbreaks.
ISSN:2150-7511