Tembusu virus induces lipid droplet accumulation to facilitate viral replication in neuronal cells via AMPK-mediated ATGL suppression
Year: 2026
Type: article
Abstract: Tembusu virus (TMUV) is a neurotropic avian flavivirus that causes viral encephalitis and egg-drop syndrome in ducks, resulting in significant economic losses in duck-producing regions in Asia. Lipid droplets (LDs) are organelles derived from the endoplasmic reticulum that primarily store neutral lipids and are involved in viral replication and pathogenesis. However, little is known about the roles of LDs in TMUV replication and neuropathogenesis. Here, we report that TMUV infection increased triglyceride (TG) levels and LD accumulation in mouse neuroblastoma cells (Neuro-2a). Inhibiting TG synthesis and LD accumulation with specific drugs reduced TMUV replication, whereas oleic acid (OA) supplementation increased LD accumulation and enhanced viral replication, indicating that LDs promote TMUV replication. Furthermore, in TMUV-infected ICR mice or goslings, we assessed LD accumulation in brain tissues and its impact on viral replication and pathology. TMUV infection increased TG levels and LD accumulation in the brain. Inhibiting LD accumulation reduced viral replication and alleviated lesions, whereas enhancing LD accumulation had the opposite effects, indicating that LDs promote TMUV neuropathogenesis. We further explored the mechanism underlying TMUV-induced LD accumulation and revealed that TMUV downregulated the lipolytic enzyme adipocyte triglyceride lipase (ATGL). ATGL overexpression reduced TG production and LD accumulation, thereby inhibiting TMUV replication, whereas ATGL knockdown had the opposite effects. Moreover, TMUV activated AMP-activated protein kinase (AMPK) signalling to suppress ATGL expression, leading to increased TG levels and LD accumulation, thereby increasing viral replication. Collectively, these findings indicate that TMUV infection induced LD accumulation via AMPK-mediated ATGL suppression to promote viral replication, and that LD accumulation contributed to TMUV neuropathogenesis.
Source: Veterinary Research
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,390
OpenAlex ID: W7225271228