Lactate facilitates largemouth bass virus replication by promoting cholesterol biosynthesis

Area of Science:

• Virology
• Immunology
• Metabolic research

Background:

• Viruses exploit host cell metabolism for replication, impacting immunity.
• Largemouth bass virus (LMBV) causes significant economic losses in aquaculture.
• The metabolic reprogramming during LMBV infection is not well understood.

Purpose of the Study:

• To investigate the role of cellular metabolism in LMBV replication.
• To elucidate the mechanisms by which LMBV affects host metabolic pathways.
• To identify potential metabolic targets for controlling LMBV infection.

Main Methods:

• In vitro and in vivo studies of LMBV-infected cells and fish.
• Analysis of viral replication under conditions of altered glycolysis and lactate levels.
• Assessment of host immune responses, including interferon signaling.
• Investigation of cholesterol biosynthesis pathways.

Main Results:

• LMBV infection significantly increased aerobic glycolysis in host cells.
• Glucose supplementation enhanced LMBV replication, while glycolysis inhibitors reduced it.
• Exogenous lactate promoted LMBV replication, viral gene expression, and protein synthesis.
• Lactate suppressed the poly(I:C)-induced interferon response and promoted cholesterol biosynthesis.
• Lactate-induced cholesterol synthesis may inhibit IRF3 phosphorylation and reduce interferon-stimulated gene expression.

Conclusions:

• LMBV manipulates host glycolysis to fuel its replication.
• Lactate plays a crucial role in facilitating LMBV replication.
• Lactate promotes viral spread by enhancing cholesterol biosynthesis and inhibiting host antiviral immunity.
• Metabolic reprogramming is a key strategy employed by LMBV during infection.