Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits Human Cytomegalovirus Infection in Multiple Cell Types

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Human cytomegalovirus (HCMV) is a significant cause of birth defects and poses risks to immunocompromised individuals.
• Autophagy induction has previously shown promise in inhibiting various viral infections.
• HCMV infection can alter cellular pathways, complicating traditional therapeutic approaches.

Purpose of the Study:

• To investigate if constitutive activation of autophagy could inhibit HCMV replication.
• To explore trehalose, an mTOR-independent autophagy inducer, as a potential therapeutic agent against HCMV.
• To assess trehalose's efficacy across different human cell types targeted by HCMV.

Main Methods:

• Treatment of human fibroblasts, endothelial cells, and neural cells with trehalose.
• Induction of autophagy using trehalose via an mTOR-independent pathway.
• Analysis of HCMV gene expression, viral production, and effects on neural cell growth.

Main Results:

• Trehalose successfully induced autophagy in all tested human cell types.
• HCMV gene expression and cell-free virus production were significantly inhibited by trehalose.
• Trehalose also reduced cell-associated HCMV, neurite growth inhibition, and cytomegaly in neural cells.

Conclusions:

• Trehalose effectively activates autophagy and inhibits HCMV replication through an mTOR-independent mechanism.
• This study provides a proof-of-concept for using natural products to target host pathways against HCMV.
• Trehalose represents a potential novel therapeutic strategy for managing HCMV diseases, minimizing resistance development.