Triacylglycerol metabolism is a novel target to combat West Nile virus infection.

Authors

Flavia Caridi, Patricia Mingo-Casas, Ana Esteban, Teresa Poderoso, Nereida Jiménez de Oya, Eva Calvo-Pinilla, Bo Zhang, Eva-María Priego, María-Jesús Pérez-Pérez, Ana-Belén Blázquez, Miguel A Martín-Acebes

Published in

Emerging microbes & infections. Pages 2728216. Sep 01, 2026. Epub Sep 01, 2026.

Abstract

West Nile virus (WNV) is a zoonotic Orthoflavivirus transmitted by mosquitoes that is responsible for outbreaks of meningitis and encephalitis worldwide. Driven by climate change, WNV has expanded as a global public health concern, particularly in temperate regions. However, there are still no specific approved therapies, reinforcing the need for antiviral development. Previous works have documented that WNV multiplication strictly depends on certain cellular lipids. To identify novel lipid-related therapeutic targets, we analyzed the infection driven alterations in the CNS lipidome, the primary tissue supporting WNV replication. Our results indicated that the major alterations in the brain lipid content of WNV-infected mice corresponded to triacylglycerols (TAGs). Moreover, transcriptomic analysis showed that infected brains underwent changes in the expression of TAG metabolism. Supplementation with exogenous fatty acids increased lipid droplets (LD) content and promoted viral replication in cell culture models. On the contrary, pharmacological intervention in TAG metabolism using diacylglycerol acyltransferase inhibitors (DGATi) suppressed WNV multiplication in cell culture models. As a proof-of-concept of the therapeutic potential of DGATi, treatment of mice with A922500 reduced viral burden in the brain and proinflammatory cytokine production. Overall, our results unveil the importance of LDs and glycerolipid metabolism for WNV and highlight the potential of therapeutic interventions targeting this pathway to control viral replication and neuroinflammation.

PMID:
42678221
Bibliographic data and abstract were imported from PubMed on 01 Sep 2026.

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