The circadian clock gene CYCLE as a potential target for disrupting blood-feeding behavior in the mosquito Culex pipiens

BACKGROUND: C. pipiens blood feeding rhythm exhibits a circadian rhythm that have the ability to persist under absent of environmental cues, consistent with endogenous control. Variations observed in the blood feeding rhythm is accompanied by changes in CYCLE (CYC) expression and olfactory sensitivity, supporting a role for CYC in pathways related to feeding propensity control. In our study, we explore the endogenous circadian control of blood feeding and the effects of mistimed feeding. RESULTS: The blood-feeding rhythm of C. pipiens is governed by an endogenous circadian clock, wherein the variations observed in blood feeding propensity is accompanied by coordinated changes in CYCLE expression and the olfactory sensitivity. We observed a light-induced masking effect that can elevate feeding propensity in subjective daytime in the absence of light, suggesting acute involvement of light in feeding regulation. Under extended starvation induced molecular stress, olfactory sensitivity was reduced along with variations in CYC expression, that is consistent with an olfactory shutdown under extreme metabolic stress. The proposed mechanism placed CYC as a molecular mediator to shut down the olfactory system in mosquitoes in response to extreme metabolic stress. We confirmed through CYCLE knockdown and behavioral assays that the loss of function of CYCLE can alter the feeding propensity in mosquitoes. We also found that mistimed feeding severely compromises mosquito reproductive health and notably evokes compensatory mechanisms. CONCLUSIONS: This study provides evidence for endogenous regulation in the blood-feeding behavior of C. pipiens, from host-seeking through olfaction to reproductive fitness. The observed changes in blood feeding rhythm are associate with the light conditions provided, and the underlying rhythm is governed through an internal clock, including core clock component CYCLE and accompanied by the rhythmic changes in small neuropeptide F expression. Through our study, we provide insights into complex genetics involved in chronobiology that control mosquito biting behaviour and reveal a novel target in chronobiology-based vector control strategies aimed at reducing mosquito-human contact.