Investigating Fatty Acid Influence on West Nile Virus in Mosquitoes and Birds

Vector-borne diseases, including Zika virus (ZIKV), Dengue virus (DENV), and West Nile virus (WNV), pose considerable global health threats, accounting for over 400 million infections and more than 700,000 deaths annually. Many vector-borne diseases are within the Flaviviridae family. Despite this, effective treatments have not been found for some flaviviruses. Flaviviruses exploit host cellular machinery to facilitate their replication and survival, reprogramming metabolic pathways, including lipid metabolism. Lipids play essential roles in the viral life cycle, providing structural components for the viral envelope, enabling membrane rearrangements for replication complexes, and supplying energy resources necessary for particle assembly. Targeting lipid metabolism is a potential therapeutic avenue against flavivirus infections. Disrupting lipid synthesis and utilization markedly impairs viral replication and reduces infection severity. Among lipid-targeting interventions, specific fatty acids including palmitoleate have emerged as promising antiviral agents. Palmitoleate, an omega-7 monounsaturated fatty acid, has provoked attention for its dual antiviral and anti-inflammatory effects. Palmitoleate exhibits antiviral properties, including the ability to disrupt viral replication, mitigate endoplasmic reticulum (ER) stress, and modulate host immune responses. Found naturally in dietary sources like sea buckthorn oil and macadamia nuts, palmitoleate notably reduces ZIKV replication by targeting the viral envelope protein and modulating host lipid pathways. To determine if palmitoleate’s effects are broad, we extend previous studies with ZIKV to understand protective effects during WNV infection. Furthermore, to examine the one health advantage of using a nutritional route as therapeutic avenues targeting vector species of WNV, we utilize Culex tarsalis and Gallus gallus cells. Palmitoleate demonstrated a protective effect in both cell lines, maintaining ATP levels and cell viability, while two other fatty acids, palmitate and stearic acid, exhibited toxicity at higher concentrations. Palmitoleate’s protective effects suggest that palmitoleate could serve as a potential antiviral agent while palmitate and stearic acid could control infected vectors through toxicity through nutritional supplementation.