Cholesterol Modulation Attenuates the AD-like Phenotype Induced by Herpes Simplex Virus Type 1 Infection

Area of Science:

• Neuroscience
• Virology
• Cell Biology

Background:

• Cholesterol is vital for cell membrane function and implicated in neurodegenerative disorders like Alzheimer's disease (AD).
• Herpes simplex virus type 1 (HSV-1) infection has been shown to induce an AD-like phenotype in cellular models.

Purpose of the Study:

• To investigate the role of cholesterol in HSV-1-induced neurodegeneration.
• To determine how modulating cellular cholesterol levels affects HSV-1 infection and AD-like pathology.

Main Methods:

• Utilized neuroblastoma cell lines (SK-N-MC and N2a).
• Manipulated cellular cholesterol levels using methyl-beta-cyclodextrin (MβCD).
• Assessed HSV-1 infection stages, cholesterol accumulation, and AD-related markers (amyloid-beta and phosphorylated tau).

Main Results:

• HSV-1 infection led to intracellular cholesterol accumulation in endolysosomal/autophagic compartments.
• MβCD treatment reversed cholesterol accumulation and inhibited HSV-1 infection at multiple stages.
• MβCD alleviated AD-like features, including lysosomal dysfunction and accumulation of amyloid-beta and phosphorylated tau.

Conclusions:

• Cellular cholesterol homeostasis is critical for HSV-1 infection and the development of neurodegeneration.
• Targeting cholesterol metabolism may offer a therapeutic strategy for managing HSV-1-induced neurodegenerative conditions, including Alzheimer's disease.