The Cholesterol Transport Inhibitor U18666A Interferes with Pseudorabies Virus Infection
1Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA.
Viruses
|July 27, 2022
Summary
Lysosomal cholesterol homeostasis is crucial for alphaherpesvirus infection. Inhibiting this process with U18666A significantly reduces pseudorabies virus (PRV) production, suggesting a key role for cellular cholesterol in viral replication.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Lysosomal cholesterol homeostasis is vital for many viral infections.
- The specific role of lysosomal cholesterol in alphaherpesvirus replication remains largely uncharacterized.
Purpose of the Study:
- To investigate the impact of lysosomal cholesterol disruption on pseudorabies virus (PRV) infection.
- To determine if modulating lysosomal cholesterol levels affects PRV replication and particle release.
Main Methods:
- Treatment of target cells and virions with the lysosomal cholesterol transport inhibitor U18666A.
- Assessment of infectious virus particle production and release.
- Utilizing cyclodextrin derivatives (HPβCD, HPγCD) to rescue cholesterol accumulation and viral inhibition.
Main Results:
- U18666A treatment significantly reduced infectious PRV particle production and suppressed virus release.
- Inhibiting cellular cholesterol transport with U18666A, but not direct virion treatment, impaired PRV yield.
- HPβCD and HPγCD treatments rescued both U18666A-induced cholesterol accumulation and PRV production inhibition.
Conclusions:
- Lysosomal cholesterol homeostasis is essential for efficient PRV replication.
- U18666A interferes with PRV infection by disrupting cellular functions, potentially including lysosomal cholesterol transport.
- Targeting lysosomal cholesterol pathways represents a potential strategy against alphaherpesvirus infections.
