25HC Depleted PMs-Accessible Cholesterol to Restrict SFTSV Entry and Infectious-EVs Mediated Infection

Area of Science:

• Virology
• Infectious Diseases
• Lipid Metabolism

Background:

• Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging tick-borne viral illness.
• Caused by a novel Bunyaviridae virus (Banda virus), SFTS presents with high fever, thrombocytopenia, and leukopenia, leading to high mortality.
• No specific antiviral treatments are currently available for SFTS.

Purpose of the Study:

• To identify potential therapeutic agents against SFTSV.
• To investigate the role of lipid metabolism in SFTSV infection and dissemination.
• To explore the antiviral activity of natural lipid metabolites.

Main Methods:

• Investigated the effect of 25-Hydroxycholesterol (25HC) on SFTSV.
• Assessed the impact of 25HC on acetyl-CoA-cholesterol acyltransferase (ACAT) activity.
• Examined the role of 25HC in inhibiting extracellular vesicle-mediated virus spread.

Main Results:

• 25-Hydroxycholesterol (25HC) inhibited SFTSV entry into host cells.
• 25HC activated ACAT, altering cholesterol translocation between cytoplasm and plasma membranes.
• 25HC reduced extracellular vesicle-mediated SFTSV dissemination.

Conclusions:

• 25HC modulates lipid metabolism to reduce accessible cholesterol at the plasma membrane.
• This mechanism inhibits both direct virion infection and extracellular vesicle-mediated spread of SFTSV.
• 25HC represents a potential therapeutic strategy to reduce SFTSV dissemination.