Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis

Area of Science:

• Virology
• Cellular Metabolism
• Immunology

Background:

• Viral replication is increasingly linked to host cell metabolic reprogramming.
• Understanding how classical swine fever virus (CSFV) alters host metabolism is crucial for controlling classical swine fever (CSF).

Purpose of the Study:

• To investigate the effects of CSFV infection on host cell metabolism, specifically focusing on glycolysis and its downstream consequences.
• To elucidate the mechanisms by which metabolic alterations facilitate CSFV replication and impact the host immune response.

Main Methods:

• Utilized PK-15 cells infected with CSFV.
• Assessed the impact of glycolysis inhibitors (2-deoxy-d-glucose) and enzyme disruptors (PFKL, LDHA) on viral replication.
• Investigated the role of lactate and its connection to cholesterol biosynthesis and the type I interferon response.

Main Results:

• CSFV infection significantly enhanced aerobic glycolysis in PK-15 cells.
• Inhibition of glycolysis or key glycolytic enzymes reduced CSFV replication.
• Lactate accumulation, independent of the pentose phosphate pathway and TCA cycle, was vital for CSFV replication.
• Lactate promoted cholesterol biosynthesis, which aided CSFV replication and impaired the type I interferon response.
• Disrupting cholesterol synthesis counteracted the effects of lactate on CSFV replication.

Conclusions:

• CSFV infection induces metabolic reprogramming, characterized by enhanced glycolysis and lactate production.
• Lactate plays a critical role in facilitating CSFV replication through cholesterol biosynthesis and immune evasion.
• These findings offer deeper insights into the pathological mechanisms of CSFV and potential targets for intervention.