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Updated: Mar 3, 2026

Ex Vivo Infection of Murine Epidermis with Herpes Simplex Virus Type 1
Published on: August 24, 2015
Cellular Cholesterol Facilitates the Postentry Replication Cycle of Herpes Simplex Virus 1
George A Wudiri1, Anthony V Nicola2
1Department of Veterinary Microbiology and Pathology and Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Cholesterol is vital for herpes simplex virus 1 (HSV-1) replication beyond entry, impacting viral synthesis and spread. Reducing cholesterol impairs HSV-1 production and cell-to-cell transmission.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Cholesterol is essential for cell membrane integrity and herpes simplex virus 1 (HSV-1) entry.
- Previous studies highlighted cellular cholesterol's role in HSV-1 entry.
- The precise stages of the HSV-1 replicative cycle dependent on cholesterol remain incompletely understood.
Purpose of the Study:
- To investigate the role of cellular cholesterol in HSV-1 replication post-entry.
- To determine if cholesterol impacts viral capsid transport, synthesis, or release.
- To compare the infectivity of cholesterol-depleted virions versus cholesterol-containing virions.
Main Methods:
- HSV-1 infected Vero cells were treated with methyl beta-cyclodextrin to reduce cholesterol levels.
- HSV-1 propagation was studied in DHCR24-/- fibroblasts, which synthesize desmosterol instead of cholesterol.
- Viral capsid transport, plaque formation, viral protein synthesis, and virion release were analyzed.
Main Results:
- Cholesterol reduction impaired HSV-1 replication at stages after capsid transport to the nucleus, affecting synthesis and release.
- Virions produced in cholesterol-depleted cells (HSVdes) showed similar infectivity per genome but were released at lower quantities.
- Cholesterol reduction significantly inhibited cell-to-cell spread of HSV-1 infection.
Conclusions:
- Cellular cholesterol plays critical roles in HSV-1 replication beyond viral entry, including viral synthesis and release.
- The hydrocarbon tail of cholesterol appears important for efficient viral synthesis.
- Cholesterol is essential for efficient cell-to-cell spread of HSV-1, indicating multiple functions in the viral life cycle.
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